Ubiquitination and De-Ubiquitination in the Synthesis of Cow Milk Fat: Reality and Prospects
Abstract
:1. Introduction
2. Ubiquitination and De-Ubiquitination Systems
2.1. Ubiquitinase and Ubiquitination Reactions
2.2. Ubiquitin–Substrate Linkages
2.3. Ubiquitin-26S Proteasome System (UPS)
2.4. De-Ubiquitinating Enzymes (DUBs) and De-Ubiquitinating Systems
3. Ubiquitination and De-Ubiquitination Modifications Are Closely Related to Milk Fat Synthesis in Dairy Cows
3.1. Overview of Milk Fat Synthesis
3.2. Ubiquitination and De-Ubiquitination during Fatty Acid Transport
3.3. Ubiquitination and De-Ubiquitination in the De Novo Synthesis of Fatty Acids
3.4. Ubiquitination and De-Ubiquitination in the Desaturation of Fatty Acids and Lipid Droplet Formation
4. Natural Plant Extracts Regulate Milk Fat Synthesis by Ubiquitination Modification
5. Ubiquitination and De-Ubiquitination Modification Linked to Cows’ Breast Health
6. Concluding Remarks and Outlook for the Future
Author Contributions
Funding
Conflicts of Interest
References
- Bernard, L.; Leroux, C.; Chilliard, Y. Expression and Nutritional Regulation of Lipogenic Genes in the Ruminant Lactating Mammary Gland. In Bioactive Components of Milk; Bösze, Z., Ed.; Springer: New York, NY, USA, 2008; pp. 67–108. [Google Scholar]
- Mu, T.; Hu, H.; Ma, Y.; Feng, X.; Zhang, J.; Gu, Y. Regulation of Key Genes for Milk Fat Synthesis in Ruminants. Front. Nutr. 2021, 8, 765147. [Google Scholar] [CrossRef]
- Bullock, J.B. Analysis of Milk Production Costs Using Cross-Section Data: The Problem of Converting Observed Quantities of Milk to a Standard Butterfat Content. Am. J. Agric. Econ. 1971, 53, 323–324. [Google Scholar] [CrossRef]
- Wilkinson, K.D. The discovery of ubiquitin-dependent proteolysis. Proc. Natl. Acad. Sci. USA 2005, 102, 15280–15282. [Google Scholar] [CrossRef] [PubMed]
- Callis, J. The Ubiquitination Machinery of the Ubiquitin System. Arab. Book 2014, 2014, e0174. [Google Scholar] [CrossRef]
- Allan, D.C.; Phillips, J.C. Why Ubiquitin Has Not Evolved. Int. J. Mol. Sci. 2017, 18, 1995. [Google Scholar] [CrossRef] [PubMed]
- von der Lehr, N.; Johansson, S.; Wu, S.; Bahram, F.; Castell, A.; Cetinkaya, C.; Hydbring, P.; Weidung, I.; Nakayama, K.; Nakayama, K.I.; et al. The F-Box Protein Skp2 Participates in c-Myc Proteosomal Degradation and Acts as a Cofactor for c-Myc-Regulated Transcription. Mol. Cell 2003, 11, 1189–1200. [Google Scholar] [CrossRef]
- Kim, S.Y.; Herbst, A.; Tworkowski, K.A.; Salghetti, S.E.; Tansey, W.P. Skp2 Regulates Myc Protein Stability and Activity. Mol. Cell 2003, 11, 1177–1188. [Google Scholar] [CrossRef] [PubMed]
- Haq, S.; Ramakrishna, S. Deubiquitylation of deubiquitylases. Open Biol. 2017, 7, 170016. [Google Scholar] [CrossRef]
- Shi, Y.; Chan, D.W.; Jung, S.Y.; Malovannaya, A.; Wang, Y.; Qin, J. A Data Set of Human Endogenous Protein Ubiquitination Sites. Mol. Cell. Proteom. 2011, 10, M110.002089. [Google Scholar] [CrossRef]
- Dagar, G.; Kumar, R.; Yadav, K.K.; Singh, M.; Pandita, T.K. Ubiquitination and deubiquitination: Implications on cancer therapy. Biochim. Et Biophys. Acta (BBA)—Gene Regul. Mech. 2023, 1866, 194979. [Google Scholar] [CrossRef]
- Liu, L.; Jiang, L.; Ding, X.-D.; Liu, J.-F.; Zhang, Q. The regulation of glucose on milk fat synthesis is mediated by the ubiquitin-proteasome system in bovine mammary epithelial cells. Biochem. Biophys. Res. Commun. 2015, 465, 59–63. [Google Scholar] [CrossRef] [PubMed]
- Lee, J. Function of Deubiquitinating Enzyme USP1 in Adipogenesis. Diabetes 2018, 67, 284-LB. [Google Scholar] [CrossRef]
- Liu, L.; Zhang, Q. Identification and functional analysis of candidate gene VPS28 for milk fat in bovine mammary epithelial cells. Biochem. Biophys. Res. Commun. 2019, 510, 606–613. [Google Scholar] [CrossRef] [PubMed]
- Cai, J.; Culley, M.K.; Zhao, Y.; Zhao, J. The role of ubiquitination and deubiquitination in the regulation of cell junctions. Protein Cell 2017, 9, 754–769. [Google Scholar] [CrossRef]
- Dye, B.T.; Schulman, B.A. Structural mechanisms underlying posttranslational modification by ubiquitin-like proteins. Annu. Rev. Biophys. Biomol. Struct. 2007, 36, 131–150. [Google Scholar] [CrossRef]
- Deshaies, R.J.; Joazeiro, C.A. RING domain E3 ubiquitin ligases. Annu. Rev. Biochem. 2009, 78, 399–434. [Google Scholar] [CrossRef]
- Haas, A.L.; Rose, I.A. The mechanism of ubiquitin activating enzyme. A kinetic and equilibrium analysis. J. Biol. Chem. 1982, 257, 10329–10337. [Google Scholar] [CrossRef]
- Haas, A.L.; Warms, J.V.; Hershko, A.; Rose, I.A. Ubiquitin-activating enzyme. Mechanism and role in protein-ubiquitin conjugation. J. Biol. Chem. 1982, 257, 2543–2548. [Google Scholar] [CrossRef]
- Liu, W.; Tang, X.; Qi, X.; Fu, X.; Ghimire, S.; Ma, R.; Li, S.; Zhang, N.; Si, H. The Ubiquitin Conjugating Enzyme: An Important Ubiquitin Transfer Platform in Ubiquitin-Proteasome System. Int. J. Mol. Sci. 2020, 21, 2894. [Google Scholar] [CrossRef]
- Swatek, K.N.; Komander, D. Ubiquitin modifications. Cell Res. 2016, 26, 399–422. [Google Scholar] [CrossRef]
- Pickart, C.M.; Eddins, M.J. Ubiquitin: Structures, functions, mechanisms. Biochim. Et Biophys. Acta (BBA)—Mol. Cell Res. 2004, 1695, 55–72. [Google Scholar] [CrossRef]
- Sharma, B.; Joshi, D.; Yadav, P.K.; Gupta, A.K.; Bhatt, T.K. Role of Ubiquitin-Mediated Degradation System in Plant Biology. Front. Plant Sci. 2016, 7, 806. [Google Scholar] [CrossRef] [PubMed]
- Strack, B.; Calistri, A.; Accola, M.A.; Palù, G.; Göttlinger, H.G. A role for ubiquitin ligase recruitment in retrovirus release. Proc. Natl. Acad. Sci. USA 2000, 97, 13063–13068. [Google Scholar] [CrossRef]
- Koganti, P.; Levy-Cohen, G.; Blank, M. Smurfs in Protein Homeostasis, Signaling, and Cancer. Front. Oncol. 2018, 8, 295. [Google Scholar] [CrossRef] [PubMed]
- Toma-Fukai, S.; Hibi, R.; Naganuma, T.; Sakai, M.; Saijo, S.; Shimizu, N.; Matsumoto, M.; Shimizu, T. Crystal structure of GCN5 PCAF N-terminal domain reveals atypical ubiquitin ligase structure. J. Biol. Chem. 2020, 295, 14630–14639. [Google Scholar] [CrossRef] [PubMed]
- Ye, Y.; Rape, M. Building ubiquitin chains: E2 enzymes at work. Nat. Rev. Mol. Cell Biol. 2009, 10, 755–764. [Google Scholar] [CrossRef]
- Behrends, C.; Harper, J.W. Constructing and decoding unconventional ubiquitin chains. Nat. Struct. Mol. Biol. 2011, 18, 520–528. [Google Scholar] [CrossRef]
- Kim, D.-Y.; Scalf, M.; Smith, L.M.; Vierstra, R.D. Advanced Proteomic Analyses Yield a Deep Catalog of Ubiquitylation Targets in Arabidopsis. Plant Cell 2013, 25, 1523–1540. [Google Scholar] [CrossRef]
- Husnjak, K.; Dikic, I. Ubiquitin-binding proteins: Decoders of ubiquitin-mediated cellular functions. Annu. Rev. Biochem. 2012, 81, 291–322. [Google Scholar] [CrossRef]
- Tanno, H.; Komada, M. The ubiquitin code and its decoding machinery in the endocytic pathway. J. Biochem. 2013, 153, 497–504. [Google Scholar] [CrossRef]
- Genschik, P. RPN10: A Case Study for Ubiquitin Binding Proteins and More. Plant Cell 2019, 31, 1398–1399. [Google Scholar] [CrossRef]
- Kimura, Y.; Tanaka, K. Regulatory mechanisms involved in the control of ubiquitin homeostasis. J. Biochem. 2010, 147, 793–798. [Google Scholar] [CrossRef] [PubMed]
- Mukhopadhyay, D.; Riezman, H. Proteasome-Independent Functions of Ubiquitin in Endocytosis and Signaling. Science 2007, 315, 201–205. [Google Scholar] [CrossRef]
- Berndsen, C.E.; Wolberger, C. New insights into ubiquitin E3 ligase mechanism. Nat. Struct. Mol. Biol. 2014, 21, 301–307. [Google Scholar] [CrossRef]
- Bergler, J.; Hoth, S. Plant U-box armadillo repeat proteins AtPUB18 and AtPUB19 are involved in salt inhibition of germination in Arabidopsis. Plant Biol. 2011, 13, 725–730. [Google Scholar] [CrossRef] [PubMed]
- Rahman, S.; Wolberger, C. Breaking the K48-chain: Linking ubiquitin beyond protein degradation. Nat. Struct. Mol. Biol. 2024, 31, 216–218. [Google Scholar] [CrossRef] [PubMed]
- Yau, R.G.; Doerner, K.; Castellanos, E.R.; Haakonsen, D.L.; Werner, A.; Wang, N.; Yang, X.W.; Martinez-Martin, N.; Matsumoto, M.L.; Dixit, V.M.; et al. Assembly and Function of Heterotypic Ubiquitin Chains in Cell-Cycle and Protein Quality Control. Cell 2017, 171, 918–933, e920. [Google Scholar] [CrossRef]
- Kulathu, Y.; Komander, D. Atypical ubiquitylation—The unexplored world of polyubiquitin beyond Lys48 and Lys63 linkages. Nat. Rev. Mol. Cell Biol. 2012, 13, 508–523. [Google Scholar] [CrossRef]
- Davidson, K.; Pickering, A.M. The proteasome: A key modulator of nervous system function, brain aging, and neurodegenerative disease. Front. Cell Dev. Biol. 2023, 11, 1124907. [Google Scholar] [CrossRef]
- Matyskiela, M.E.; Lander, G.C.; Martin, A. Conformational switching of the 26S proteasome enables substrate degradation. Nat. Struct. Mol. Biol. 2013, 20, 781–788. [Google Scholar] [CrossRef]
- Förster, F.; Unverdorben, P.; Sledź, P.; Baumeister, W. Unveiling the Long-Held Secrets of the 26S Proteasome. Structure 2013, 21, 1551–1562. [Google Scholar] [CrossRef] [PubMed]
- Geng, F.; Wenzel, S.; Tansey, W.P. Ubiquitin and Proteasomes in Transcription. Annu. Rev. Biochem. 2012, 81, 177–201. [Google Scholar] [CrossRef]
- Smalle, J.; Vierstra, R.D. The ubiquitin 26S proteasome proteolytic pathway. Annu. Rev. Plant Biol. 2004, 55, 555–590. [Google Scholar] [CrossRef] [PubMed]
- Gao, Z.; Gammoh, N.; Wong, P.-M.; Erdjument-Bromage, H.; Tempst, P.; Jiang, X. Processing of autophagic protein LC3 by the 20S proteasome. Autophagy 2010, 6, 126–137. [Google Scholar] [CrossRef] [PubMed]
- Wilfling, F.; Lee, C.-W.; Erdmann, P.S.; Zheng, Y.; Sherpa, D.; Jentsch, S.; Pfander, B.; Schulman, B.A.; Baumeister, W. A Selective Autophagy Pathway for Phase-Separated Endocytic Protein Deposits. Mol. Cell 2020, 80, 764–778.E7. [Google Scholar] [CrossRef]
- Nagel, M.-K.; Kalinowska, K.; Vogel, K.; Reynolds, G.D.; Wu, Z.; Anzenberger, F.; Ichikawa, M.; Tsutsumi, C.; Sato, M.H.; Kuster, B.; et al. Arabidopsis SH3P2 is an ubiquitin-binding protein that functions together with ESCRT-I and the deubiquitylating enzyme AMSH3. Proc. Natl. Acad. Sci. USA 2017, 114, E7197–E7204. [Google Scholar] [CrossRef]
- Höhfeld, J.; Cyr, D.M.; Patterson, C. From the cradle to the grave: Molecular chaperones that may choose between folding and degradation. EMBO Rep. 2001, 2, 885–890. [Google Scholar] [CrossRef]
- Seibenhener, M.L.; Babu, J.R.; Geetha, T.; Wong, H.C.; Krishna, N.R.; Wooten, M.W. Sequestosome 1/p62 Is a Polyubiquitin Chain Binding Protein Involved in Ubiquitin Proteasome Degradation. Mol. Cell. Biol. 2004, 24, 8055–8068. [Google Scholar] [CrossRef]
- Amerik, A.Y.; Hochstrasser, M. Mechanism and function of deubiquitinating enzymes. Biochim. Biophys. Acta 2004, 1695, 189–207. [Google Scholar] [CrossRef]
- Du, J.; Fu, L.; Sui, Y.; Zhang, L. The function and regulation of OTU deubiquitinases. Front. Med. 2020, 14, 542–563. [Google Scholar] [CrossRef]
- Nijman, S.M.; Luna-Vargas, M.P.; Velds, A.; Brummelkamp, T.R.; Dirac, A.M.; Sixma, T.K.; Bernards, R. A genomic and functional inventory of deubiquitinating enzymes. Cell 2005, 123, 773–786. [Google Scholar] [CrossRef] [PubMed]
- Keijzer, N.; Priyanka, A.; Stijf-Bultsma, Y.; Fish, A.; Gersch, M.; Sixma, T.K. Variety in the USP deubiquitinase catalytic mechanism. Life Sci. Alliance 2024, 7, e202302533. [Google Scholar] [CrossRef]
- Heideker, J.; Wertz, I.E. DUBs, the regulation of cell identity and disease. Biochem. J. 2015, 465, 1–26. [Google Scholar] [CrossRef]
- Peterson, B.G.; Glaser, M.L.; Rapoport, T.A.; Baldridge, R.D. Cycles of autoubiquitination and deubiquitination regulate the ERAD ubiquitin ligase Hrd1. eLife 2019, 8, e50903. [Google Scholar] [CrossRef] [PubMed]
- Huang, X.; Summers, M.K.; Pham, V.; Lill, J.R.; Liu, J.; Lee, G.; Kirkpatrick, D.S.; Jackson, P.K.; Fang, G.; Dixit, V.M. Deubiquitinase USP37 is activated by CDK2 to antagonize APC(CDH1) and promote S phase entry. Mol. Cell 2011, 42, 511–523. [Google Scholar] [CrossRef] [PubMed]
- Liu, N.; Lin, M.-M.; Wang, Y. The Emerging Roles of E3 Ligases and DUBs in Neurodegenerative Diseases. Mol. Neurobiol. 2023, 60, 247–263. [Google Scholar] [CrossRef]
- Michel, M.A.; Komander, D.; Elliott, P.R. Enzymatic Assembly of Ubiquitin Chains. In The Ubiquitin Proteasome System: Methods and Protocols; Mayor, T., Kleiger, G., Eds.; Springer: New York, NY, USA, 2018; pp. 73–84. [Google Scholar]
- Clague, M.J.; Urbé, S.; Komander, D. Breaking the chains: Deubiquitylating enzyme specificity begets function. Nat. Rev. Mol. Cell Biol. 2019, 20, 338–352. [Google Scholar] [CrossRef]
- Wang, Y.; Wang, F. Post-Translational Modifications of Deubiquitinating Enzymes: Expanding the Ubiquitin Code. Front. Pharmacol. 2021, 12, 685011. [Google Scholar] [CrossRef]
- Thum, C.; Roy, N.C.; Everett, D.W.; McNabb, W.C. Variation in milk fat globule size and composition: A source of bioactives for human health. Crit. Rev. Food Sci. Nutr. 2023, 63, 87–113. [Google Scholar] [CrossRef]
- Lindmark Månsson, H. Fatty acids in bovine milk fat. Food Nutr. Res. 2008, 52. [Google Scholar] [CrossRef]
- Jensen, R.G. The Composition of Bovine Milk Lipids: January 1995 to December 2000. J. Dairy Sci. 2002, 85, 295–350. [Google Scholar] [CrossRef] [PubMed]
- Wang, D.; Zhao, Z.; Shi, Y.; Luo, J.; Chen, T.; Xi, Q.; Zhang, Y.; Sun, J. CircEZH2 Regulates Milk Fat Metabolism through miR-378b Sponge Activity. Animals 2022, 12, 718. [Google Scholar] [CrossRef]
- Guo, Y.; Wei, Z.; Zhang, Y.; Cao, J. Research Progress on the Mechanism of Milk Fat Synthesis in Cows and the Effect of Conjugated Linoleic Acid on Milk Fat Metabolism and Its Underlying Mechanism: A Review. Animals 2024, 14, 204. [Google Scholar] [CrossRef] [PubMed]
- Harvatine, K.J.; Boisclair, Y.R.; Bauman, D.E. Recent advances in the regulation of milk fat synthesis. Animal 2009, 3, 40–54. [Google Scholar] [CrossRef]
- Chajès, V.r.; Cambot, M.; Moreau, K.; Lenoir, G.M.; Joulin, V. Acetyl-CoA Carboxylase α Is Essential to Breast Cancer Cell Survival. Cancer Res. 2006, 66, 5287–5294. [Google Scholar] [CrossRef] [PubMed]
- Tian, Z.; Zhang, Y.; Zhang, H.; Sun, Y.; Mao, Y.; Yang, Z.; Li, M. Transcriptional regulation of milk fat synthesis in dairy cattle. J. Funct. Foods 2022, 96, 105208. [Google Scholar] [CrossRef]
- West, C.E.; Bickerstaffe, R.; Annison, E.F.; Linzell, J.L. Studies on the mode of uptake of blood triglycerides by the mammary gland of the lactating goat. The uptake and incorporation into milk fat and mammary lymph of labelled glycerol, fatty acids and triglycerides. Biochem. J. 1972, 126, 477–490. [Google Scholar] [CrossRef]
- Thering, B.J.; Graugnard, D.E.; Piantoni, P.; Loor, J.J. Adipose tissue lipogenic gene networks due to lipid feeding and milk fat depression in lactating cows. J. Dairy Sci. 2009, 92, 4290–4300. [Google Scholar] [CrossRef]
- Peterson, D.G.; Matitashvili, E.A.; Bauman, D.E. The Inhibitory Effect of trans-10, cis-12 CLA on Lipid Synthesis in Bovine Mammary Epithelial Cells Involves Reduced Proteolytic Activation of the Transcription Factor SREBP-1. J. Nutr. 2004, 134, 2523–2527. [Google Scholar] [CrossRef]
- Lian, S.; Guo, J.R.; Nan, X.M.; Ma, L.; Loor, J.J.; Bu, D.P. MicroRNA Bta-miR-181a regulates the biosynthesis of bovine milk fat by targeting ACSL1. J. Dairy Sci. 2016, 99, 3916–3924. [Google Scholar] [CrossRef]
- Chang, B.H.-J.; Chan, L. Regulation of Triglyceride Metabolism. III. Emerging role of lipid droplet protein ADFP in health and disease. Am. J. Physiol. Gastrointest. Liver Physiol. 2007, 292, G1465–G1468. [Google Scholar] [CrossRef] [PubMed]
- Xin, Z.; Zhang, T.; Lu, Q.; Yang, Z.; Chen, Z. Progress of m6A Methylation in Lipid Metabolism in Humans and Animals. Agriculture 2022, 12, 1683. [Google Scholar] [CrossRef]
- Yang, X.; Lu, X.; Wang, L.; Bai, L.; Yao, R.; Jia, Z.; Ma, Y.; Chen, Y.; Hao, H.; Wu, X.; et al. Stearic acid promotes lipid synthesis through CD36/Fyn/FAK/mTORC1 axis in bovine mammary epithelial cells. Int. J. Biol. Macromol. 2023, 253, 127324. [Google Scholar] [CrossRef]
- Holloway, G.P.; Nickerson, J.G.; Lally, J.S.V.; Petrick, H.L.; Dennis, K.M.J.H.; Jain, S.S.; Alkhateeb, H.; Bonen, A. Co-overexpression of CD36 and FABPpm increases fatty acid transport additively, not synergistically, within muscle. Am. J. Physiol. Cell Physiol. 2022, 322, C546–C553. [Google Scholar] [CrossRef]
- Xu, G.; Xu, Y.; Zhang, Y.; Kao, G.; Li, J. miR-1268a Regulates Fatty Acid Metabolism by Targeting CD36 in Angiotensin II-induced Heart Failure. Cell Biochem. Biophys. 2024, 82, 1193–1201. [Google Scholar] [CrossRef] [PubMed]
- Karunakaran, U.; Elumalai, S.; Moon, J.-S.; Won, K.-C. CD36 Signal Transduction in Metabolic Diseases: Novel Insights and Therapeutic Targeting. Cells 2021, 10, 1833. [Google Scholar] [CrossRef]
- Smith, J.; Su, X.; El-Maghrabi, R.; Stahl, P.D.; Abumrad, N.A. Opposite regulation of CD36 ubiquitination by fatty acids and insulin: Effects on fatty acid uptake. J. Biol. Chem. 2008, 283, 13578–13585. [Google Scholar] [CrossRef] [PubMed]
- Zeng, M.; Wei, X.; He, Y.; Yang, Y. Ubiquitin-specific protease 11-mediated CD36 deubiquitination acts on C1q/TNF-related protein 9 against atherosclerosis. ESC Heart Fail 2023, 10, 2499–2509. [Google Scholar] [CrossRef]
- Liu, L.; Zhang, Q. Comparative proteome analysis reveals VPS28 regulates milk fat synthesis through ubiquitylation in bovine mammary epithelial cells. PeerJ 2020, 8, e9542. [Google Scholar] [CrossRef]
- Zhang, F.; Xia, X.; Chai, R.; Xu, R.; Xu, Q.; Liu, M.; Chen, X.; Liu, B.; Liu, S.; Liu, N. Inhibition of USP14 suppresses the formation of foam cell by promoting CD36 degradation. J. Cell. Mol. Med. 2020, 24, 3292–3302. [Google Scholar] [CrossRef]
- Xia, X.; Xu, Q.; Liu, M.; Chen, X.; Liu, X.; He, J.; Hu, T.; Yu, C.; Huang, H.; Liu, S.; et al. Deubiquitination of CD36 by UCHL1 promotes foam cell formation. Cell Death Dis. 2020, 11, 636. [Google Scholar] [CrossRef] [PubMed]
- Schrader, E.K.; Harstad, K.G.; Matouschek, A. Targeting proteins for degradation. Nat. Chem. Biol. 2009, 5, 815–822. [Google Scholar] [CrossRef]
- Young, P.A.; Senkal, C.E.; Suchanek, A.L.; Grevengoed, T.J.; Lin, D.D.; Zhao, L.; Crunk, A.E.; Klett, E.L.; Füllekrug, J.; Obeid, L.M.; et al. Long-chain acyl-CoA synthetase 1 interacts with key proteins that activate and direct fatty acids into niche hepatic pathways. J. Biol. Chem. 2018, 293, 16724–16740. [Google Scholar] [CrossRef] [PubMed]
- Bionaz, M.; Loor, J.J. ACSL1, AGPAT6, FABP3, LPIN1, and SLC27A6 Are the Most Abundant Isoforms in Bovine Mammary Tissue and Their Expression Is Affected by Stage of Lactation. J. Nutr. 2008, 138, 1019–1024. [Google Scholar] [CrossRef] [PubMed]
- Qiu, M.; Yan, W.; Liu, M. YAP Facilitates NEDD4L-Mediated Ubiquitination and Degradation of ACSL4 to Alleviate Ferroptosis in Myocardial Ischemia-Reperfusion Injury. Can. J. Cardiol. 2023, 39, 1712–1727. [Google Scholar] [CrossRef]
- Chen, Z.; Shi, H.; Sun, S.; Xu, H.; Cao, D.; Luo, J. MicroRNA-181b suppresses TAG via target IRS2 and regulating multiple genes in the Hippo pathway. Exp. Cell Res. 2016, 348, 66–74. [Google Scholar] [CrossRef]
- Li, A.; Wu, L.; Wang, X.; Xin, Y.; Zan, L. Tissue expression analysis, cloning and characterization of the 5′-regulatory region of the bovine FABP3 gene. Mol. Biol. Rep. 2016, 43, 991–998. [Google Scholar] [CrossRef]
- Li, P.; Yu, M.; Zhou, C.; Qi, H.; Wen, X.; Hou, X.; Li, M.; Gao, X. FABP5 is a critical regulator of methionine- and estrogen-induced SREBP-1c gene expression in bovine mammary epithelial cells. J. Cell. Physiol. 2019, 234, 537–549. [Google Scholar] [CrossRef]
- Chung, S.S.; Ahn, B.Y.; Kim, M.; Kho, J.H.; Jung, H.S.; Park, K.S. SUMO modification selectively regulates transcriptional activity of peroxisome-proliferator-activated receptor γ in C2C12 myotubes. Biochem. J. 2010, 433, 155–161. [Google Scholar] [CrossRef]
- Li, X.; He, W.; Chen, X.; Zhang, Y.; Zhang, J.; Liu, F.; Li, J.; Zhao, D.; Xia, P.; Ma, W.; et al. TRIM45 facilitates NASH-progressed HCC by promoting fatty acid synthesis via catalyzing FABP5 ubiquitylation. Oncogene 2024, 43, 2063–2077. [Google Scholar] [CrossRef]
- You, H.; Wen, X.; Wang, X.; Zhu, C.; Chen, H.; Bu, L.; Zhang, J.; Qu, S. Derlin-1 ameliorates nonalcoholic hepatic steatosis by promoting ubiquitylation and degradation of FABP1. Free Radic. Biol. Med. 2023, 207, 260–271. [Google Scholar] [CrossRef]
- Moslehi, A.; Hamidi-Zad, Z. Role of SREBPs in Liver Diseases: A Mini-review. J. Clin. Transl. Hepatol. 2018, 6, 332–338. [Google Scholar] [CrossRef]
- DeBose-Boyd, R.A.; Ye, J. SREBPs in Lipid Metabolism, Insulin Signaling, and Beyond. Trends Biochem. Sci. 2018, 43, 358–368. [Google Scholar] [CrossRef]
- Rincon, G.; Islas-Trejo, A.; Castillo, A.R.; Bauman, D.E.; German, B.J.; Medrano, J.F. Polymorphisms in genes in the SREBP1 signalling pathway and SCD are associated with milk fatty acid composition in Holstein cattle. J. Dairy Res. 2012, 79, 66–75. [Google Scholar] [CrossRef]
- Li, N.; Zhao, F.; Wei, C.; Liang, M.; Zhang, N.; Wang, C.; Li, Q.Z.; Gao, X.J. Function of SREBP1 in the milk fat synthesis of dairy cow mammary epithelial cells. Int. J. Mol. Sci. 2014, 15, 16998–17013. [Google Scholar] [CrossRef] [PubMed]
- Sato, R. SREBPs: Protein interaction and SREBPs. FEBS J. 2009, 276, 622–627. [Google Scholar] [CrossRef] [PubMed]
- Hendrix, S.; Zelcer, N. A new SPRING in lipid metabolism. Curr. Opin. Lipidol. 2023, 34, 201–207. [Google Scholar] [CrossRef] [PubMed]
- Xu, H.; Luo, J.; Ma, G.; Zhang, X.; Yao, D.; Li, M.; Loor, J.J. Acyl-CoA synthetase short-chain family member 2 (ACSS2) is regulated by SREBP-1 and plays a role in fatty acid synthesis in caprine mammary epithelial cells. J. Cell. Physiol. 2018, 233, 1005–1016. [Google Scholar] [CrossRef]
- Kawamura, S.; Matsushita, Y.; Kurosaki, S.; Tange, M.; Fujiwara, N.; Hayata, Y.; Hayakawa, Y.; Suzuki, N.; Hata, M.; Tsuboi, M.; et al. Inhibiting SCAP/SREBP exacerbates liver injury and carcinogenesis in murine nonalcoholic steatohepatitis. J. Clin. Investig. 2022, 132, e151895. [Google Scholar] [CrossRef]
- Moon, Y.A. The SCAP/SREBP Pathway: A Mediator of Hepatic Steatosis. Endocrinol. Metab. 2017, 32, 6–10. [Google Scholar] [CrossRef]
- Sundqvist, A.; Bengoechea-Alonso, M.T.; Ye, X.; Lukiyanchuk, V.; Jin, J.; Harper, J.W.; Ericsson, J. Control of lipid metabolism by phosphorylation-dependent degradation of the SREBP family of transcription factors by SCF(Fbw7). Cell Metab. 2005, 1, 379–391. [Google Scholar] [CrossRef] [PubMed]
- Punga, T.; Bengoechea-Alonso, M.T.; Ericsson, J. Phosphorylation and Ubiquitination of the Transcription Factor Sterol Regulatory Element-binding Protein-1 in Response to DNA Binding. J. Biol. Chem. 2006, 281, 25278–25286. [Google Scholar] [CrossRef] [PubMed]
- Bolshette, N.; Ezagouri, S.; Dandavate, V.; Karavaeva, I.; Golik, M.; Wang, H.; Espenshade, P.J.; Osborne, T.F.; Han, X.; Asher, G. Carbon dioxide regulates cholesterol levels through SREBP2. PLoS Biol. 2023, 21, e3002367. [Google Scholar] [CrossRef] [PubMed]
- Sacco, J.J.; Coulson, J.M.; Clague, M.J.; Urbé, S. Emerging roles of deubiquitinases in cancer-associated pathways. IUBMB Life 2010, 62, 140–157. [Google Scholar] [CrossRef] [PubMed]
- Zhang, D.; Zaugg, K.; Mak, T.W.; Elledge, S.J. A role for the deubiquitinating enzyme USP28 in control of the DNA-damage response. Cell 2006, 126, 529–542. [Google Scholar] [CrossRef]
- Bassermann, F.; Frescas, D.; Guardavaccaro, D.; Busino, L.; Peschiaroli, A.; Pagano, M. The Cdc14B-Cdh1-Plk1 axis controls the G2 DNA-damage-response checkpoint. Cell 2008, 134, 256–267. [Google Scholar] [CrossRef]
- Maier, C.R.; Hartmann, O.; Prieto-Garcia, C.; Al-Shami, K.M.; Schlicker, L.; Vogel, F.C.E.; Haid, S.; Klann, K.; Buck, V.; Münch, C.; et al. USP28 controls SREBP2 and the mevalonate pathway to drive tumour growth in squamous cancer. Cell Death Differ. 2023, 30, 1710–1725. [Google Scholar] [CrossRef]
- Chen, L.; Lengi, A.J.; Corl, B.A. The inhibitory effect of trans-10,cis-12 conjugated linoleic acid on sterol regulatory element binding protein-1 activation in bovine mammary epithelial cells involved reduced proteasomal degradation of insulin-induced gene-1. J. Dairy Sci. 2021, 104, 11306–11316. [Google Scholar] [CrossRef]
- Kuan, Y.C.; Takahashi, Y.; Maruyama, T.; Shimizu, M.; Yamauchi, Y.; Sato, R. Ring finger protein 5 activates sterol regulatory element-binding protein 2 (SREBP2) to promote cholesterol biosynthesis via inducing polyubiquitination of SREBP chaperone SCAP. J. Biol. Chem. 2020, 295, 3918–3928. [Google Scholar] [CrossRef]
- Matsumoto, H.; Inada, S.; Kobayashi, E.; Abe, T.; Hasebe, H.; Sasazaki, S.; Oyama, K.; Mannen, H. Identification of SNPs in the FASN gene and their effect on fatty acid milk composition in Holstein cattle. Livest. Sci. 2012, 144, 281–284. [Google Scholar] [CrossRef]
- Zhang, Y.; Fan, X.; Qiu, L.; Zhu, W.; Huang, L.; Miao, Y. Liver X receptor α promotes milk fat synthesis in buffalo mammary epithelial cells by regulating the expression of FASN. J. Dairy Sci. 2021, 104, 12980–12993. [Google Scholar] [CrossRef]
- Suburu, J.; Shi, L.; Wu, J.; Wang, S.; Samuel, M.; Thomas, M.J.; Kock, N.D.; Yang, G.; Kridel, S.; Chen, Y.Q. Fatty acid synthase is required for mammary gland development and milk production during lactation. Am. J. Physiol. Endocrinol. Metab. 2014, 306, E1132–E1143. [Google Scholar] [CrossRef]
- Roy, R.; Ordovas, L.; Zaragoza, P.; Romero, A.; Moreno, C.; Altarriba, J.; Rodellar, C. Association of polymorphisms in the bovine FASN gene with milk-fat content. Anim. Genet. 2006, 37, 215–218. [Google Scholar] [CrossRef] [PubMed]
- Shen, Y.; Li, N.L.; Wang, J.; Liu, B.; Lester, S.; Li, K. TRIM56 is an essential component of the TLR3 antiviral signaling pathway. J. Biol. Chem. 2012, 287, 36404–36413. [Google Scholar] [CrossRef] [PubMed]
- Xu, S.; Wu, X.; Wang, S.; Xu, M.; Fang, T.; Ma, X.; Chen, M.; Fu, J.; Guo, J.; Tian, S.; et al. TRIM56 protects against nonalcoholic fatty liver disease by promoting the degradation of fatty acid synthase. J. Clin. Investig. 2024, 134, e166149. [Google Scholar] [CrossRef]
- Zhang, K.; Yang, C.; Zhou, X.; Liang, J.; Guo, J.; Li, M.; Zhang, Y.; Shao, S.; Sun, P.; Li, K.; et al. TRIM21 ameliorates hepatic glucose and lipid metabolic disorders in type 2 diabetes mellitus by ubiquitination of PEPCK1 and FASN. Cell. Mol. Life Sci. 2023, 80, 168. [Google Scholar] [CrossRef] [PubMed]
- Komander, D.; Clague, M.J.; Urbé, S. Breaking the chains: Structure and function of the deubiquitinases. Nat. Rev. Mol. Cell Biol. 2009, 10, 550–563. [Google Scholar] [CrossRef]
- Hanna, J.; Hathaway, N.A.; Tone, Y.; Crosas, B.; Elsasser, S.; Kirkpatrick, D.S.; Leggett, D.S.; Gygi, S.P.; King, R.W.; Finley, D. Deubiquitinating Enzyme Ubp6 Functions Noncatalytically to Delay Proteasomal Degradation. Cell 2006, 127, 99–111. [Google Scholar] [CrossRef] [PubMed]
- Lee, B.-H.; Lu, Y.; Prado, M.A.; Shi, Y.; Tian, G.; Sun, S.; Elsasser, S.; Gygi, S.P.; King, R.W.; Finley, D. USP14 deubiquitinates proteasome-bound substrates that are ubiquitinated at multiple sites. Nature 2016, 532, 398–401. [Google Scholar] [CrossRef]
- Coyne, E.S.; Bédard, N.; Gong, Y.J.; Faraj, M.; Tchernof, A.; Wing, S.S. The deubiquitinating enzyme USP19 modulates adipogenesis and potentiates high-fat-diet-induced obesity and glucose intolerance in mice. Diabetologia 2019, 62, 136–146. [Google Scholar] [CrossRef]
- Ravaut, G.; Légiot, A.; Bergeron, K.-F.; Mounier, C. Monounsaturated Fatty Acids in Obesity-Related Inflammation. Int. J. Mol. Sci. 2021, 22, 330. [Google Scholar] [CrossRef]
- Tian, H.; Luo, J.; Zhang, Z.; Wu, J.; Zhang, T.; Busato, S.; Huang, L.; Song, N.; Bionaz, M. CRISPR/Cas9-mediated Stearoyl-CoA Desaturase 1 (SCD1) Deficiency Affects Fatty Acid Metabolism in Goat Mammary Epithelial Cells. J. Agric. Food Chem. 2018, 66, 10041–10052. [Google Scholar] [CrossRef] [PubMed]
- Kato, H.; Sakaki, K.; Mihara, K. Ubiquitin-proteasome-dependent degradation of mammalian ER stearoyl-CoA desaturase. J. Cell Sci. 2006, 119, 2342–2353. [Google Scholar] [CrossRef] [PubMed]
- Li, Z.; Luo, L.; Yu, W.; Li, P.; Ou, D.; Liu, J.; Ma, H.; Sun, Q.; Liang, A.; Huang, C.; et al. PPARγ phase separates with RXRα at PPREs to regulate target gene expression. Cell Discov. 2022, 8, 37. [Google Scholar] [CrossRef]
- Kilroy, G.E.; Zhang, X.; Floyd, Z.E. PPAR-gamma AF-2 domain functions as a component of a ubiquitin-dependent degradation signal. Obesity 2009, 17, 665–673. [Google Scholar] [CrossRef] [PubMed]
- Waite, K.J.; Floyd, Z.E.; Arbour-Reily, P.; Stephens, J.M. Interferon-gamma-induced regulation of peroxisome proliferator-activated receptor gamma and STATs in adipocytes. J. Biol. Chem. 2001, 276, 7062–7068. [Google Scholar] [CrossRef]
- Lee, K.W.; Kwak, S.H.; Koo, Y.D.; Cho, Y.-K.; Lee, H.M.; Jung, H.S.; Cho, Y.M.; Park, Y.J.; Chung, S.S.; Park, K.S. F-box only protein 9 is an E3 ubiquitin ligase of PPARγ. Exp. Mol. Med. 2016, 48, e234. [Google Scholar] [CrossRef]
- Ning, Z.; Guo, X.; Liu, X.; Lu, C.; Wang, A.; Wang, X.; Wang, W.; Chen, H.; Qin, W.; Liu, X.; et al. USP22 regulates lipidome accumulation by stabilizing PPARγ in hepatocellular carcinoma. Nat. Commun. 2022, 13, 2187. [Google Scholar] [CrossRef]
- McManaman, J.L.; Zabaronick, W.; Schaack, J.; Orlicky, D.J. Lipid droplet targeting domains of adipophilin. J. Lipid Res. 2003, 44, 668–673. [Google Scholar] [CrossRef]
- Ganguly, B.; Ambwani, T.K.; Rastogi, S.K. Electronic Northern Analysis of Genes and Modeling of Gene Networks Underlying Bovine Milk Fat Production. Genet. Res. Int. 2017, 2017, 1910530. [Google Scholar] [CrossRef]
- Yuan, Y.; Li, X.; Xu, Y.; Zhao, H.; Su, Z.; Lai, D.; Yang, W.; Chen, S.; He, Y.; Li, X.; et al. Mitochondrial E3 ubiquitin ligase 1 promotes autophagy flux to suppress the development of clear cell renal cell carcinomas. Cancer Sci. 2019, 110, 3533–3542. [Google Scholar] [CrossRef]
- Liu, L.L.; Guo, A.W.; Wu, P.F.; Chen, F.F.; Yang, Y.J.; Zhang, Q. Regulation of VPS28 gene knockdown on the milk fat synthesis in Chinese Holstein dairy. Yi Chuan 2018, 40, 1092–1100. [Google Scholar] [CrossRef]
- Palmquist, D.L.; Denise Beaulieu, A.; Barbano, D.M. Feed and Animal Factors Influencing Milk Fat Composition. J. Dairy Sci. 1993, 76, 1753–1771. [Google Scholar] [CrossRef] [PubMed]
- Herve, L.; Quesnel, H.; Veron, M.; Portanguen, J.; Gross, J.J.; Bruckmaier, R.M.; Boutinaud, M. Milk yield loss in response to feed restriction is associated with mammary epithelial cell exfoliation in dairy cows. J. Dairy Sci. 2019, 102, 2670–2685. [Google Scholar] [CrossRef] [PubMed]
- Zunong, M.; Tuerhong, T.; Okamoto, M.; Hongo, A.; Hanada, M. Effects of a potato pulp silage supplement on the composition of milk fatty acids when fed to grazing dairy cows. Anim. Feed Sci. Technol. 2009, 152, 81–91. [Google Scholar] [CrossRef]
- Yu, M.-F.; Zhao, X.-M.; Cai, H.; Yi, J.-M.; Hua, G.-H. Dihydropyridine Enhances the Antioxidant Capacities of Lactating Dairy Cows under Heat Stress Condition. Animals 2020, 10, 1812. [Google Scholar] [CrossRef]
- Vanmierlo, T.; Bogie, J.F.J.; Mailleux, J.; Vanmol, J.; Lütjohann, D.; Mulder, M.; Hendriks, J.J.A. Plant sterols: Friend or foe in CNS disorders? Prog. Lipid Res. 2015, 58, 26–39. [Google Scholar] [CrossRef] [PubMed]
- Bakrim, S.; Benkhaira, N.; Bourais, I.; Benali, T.; Lee, L.-H.; El Omari, N.; Sheikh, R.A.; Goh, K.W.; Ming, L.C.; Bouyahya, A. Health Benefits and Pharmacological Properties of Stigmasterol. Antioxidants 2022, 11, 1912. [Google Scholar] [CrossRef]
- Santos, N.C.; Girik, V.; Nunes-Hasler, P. ORP5 and ORP8: Sterol Sensors and Phospholipid Transfer Proteins at Membrane Contact Sites? Biomolecules 2020, 10, 928. [Google Scholar] [CrossRef]
- Song, L.; Zhang, L.; Zhou, Y.; Shao, X.; Xu, Y.; Pei, D.; Wang, Q. ORP5 promotes tumor metastasis via stabilizing c-Met in renal cell carcinoma. Cell Death Discov. 2022, 8, 219. [Google Scholar] [CrossRef]
- Chung, W.; Ahuja, M.; McNally, B.A.; Ohman, H.K.E.; Leibow, S.; Muallem, S. The lipid transporter proteins ORP5 and ORP8 in Ca2+signaling. Biophys. J. 2022, 121, 373a. [Google Scholar] [CrossRef]
- Sun, M.; Cao, Y.; Cheng, J.; Xu, D.; Li, F.; Wang, J.; Ge, Y.; Liu, Y.; Long, X.; Guo, W.; et al. Stigmasterol Activates the mTOR Signaling Pathway by Inhibiting ORP5 Ubiquitination to Promote Milk Synthesis in Bovine Mammary Epithelial Cells. J. Agric. Food Chem. 2024, 72, 14769–14785. [Google Scholar] [CrossRef] [PubMed]
- Meng, Y.; Lyu, C.-C.; He, Y.-T.; Che, H.-Y.; Jiang, H.; Zhang, J.-B.; Tang, H.-Y.; Yuan, B. ALG5 Regulates STF-62247-Induced Milk Fat Synthesis via the mTOR Signaling Pathway. J. Agric. Food Chem. 2024, 72, 14620–14629. [Google Scholar] [CrossRef] [PubMed]
- Alonso-Castro, A.J.; Serrano-Vega, R.; Pérez Gutiérrez, S.; Isiordia-Espinoza, M.A.; Solorio-Alvarado, C.R. Myristic acid reduces skin inflammation and nociception. J. Food Biochem. 2022, 46, e14013. [Google Scholar] [CrossRef]
- Rioux, V.; Pédrono, F.; Legrand, P. Regulation of mammalian desaturases by myristic acid: N-terminal myristoylation and other modulations. Biochim. Et Biophys. Acta (BBA)—Mol. Cell Biol. Lipids 2011, 1811, 1–8. [Google Scholar] [CrossRef]
- Kummrow, E.; Hussain, M.M.; Pan, M.; Marsh, J.B.; Fisher, E.A. Myristic acid increases dense lipoprotein secretion by inhibiting apoB degradation and triglyceride recruitment. J. Lipid Res. 2002, 43, 2155–2163. [Google Scholar] [CrossRef]
- Hu, M.; Wu, P.; Guo, A.; Liu, L. Myristic Acid Regulates Triglyceride Production in Bovine Mammary Epithelial Cells through the Ubiquitination Pathway. Agriculture 2023, 13, 1870. [Google Scholar] [CrossRef]
- Aragona, K.M.; Rice, E.M.; Engstrom, M.; Erickson, P.S. Effect of β-carotene supplementation to prepartum Holstein cows on colostrum quality and calf performance. J. Dairy Sci. 2021, 104, 8814–8825. [Google Scholar] [CrossRef]
- Kong, S.; Li, J.; Pan, X.; Zhao, C.; Li, Y. Allicin regulates Sestrin2 ubiquitination to affect macrophage autophagy and senescence, thus inhibiting the growth of hepatoma cells. Tissue Cell 2024, 88, 102398. [Google Scholar] [CrossRef]
- Shuhua, Y.; Lingqi, M.; Yunlong, D.; He, T.; Yao, S.; Peng, L. Proanthocyanidins Activate Nrf2/ARE Signaling Pathway in Intestinal Epithelial Cells by Inhibiting the Ubiquitinated Degradation of Nrf2. BioMed Res. Int. 2022, 2022, 8562795. [Google Scholar] [CrossRef]
- Wang, J.; Zhang, X.; He, X.; Yang, B.; Wang, H.; Shan, X.; Li, C.; Sun, D.; Wu, R. LPS-induced reduction of triglyceride synthesis and secretion in dairy cow mammary epithelial cells via decreased SREBP1 expression and activity. J. Dairy Res. 2018, 85, 439–444. [Google Scholar] [CrossRef]
- Vailati-Riboni, M.; Coleman, D.N.; Lopreiato, V.; Alharthi, A.; Bucktrout, R.E.; Abdel-Hamied, E.; Martinez-Cortes, I.; Liang, Y.; Trevisi, E.; Yoon, I.; et al. Feeding a Saccharomyces cerevisiae fermentation product improves udder health and immune response to a Streptococcus uberis mastitis challenge in mid-lactation dairy cows. J. Anim. Sci. Biotechnol. 2021, 12, 62. [Google Scholar] [CrossRef] [PubMed]
- Zhang, M.; Bi, X. Heat Shock Proteins and Breast Cancer. Int. J. Mol. Sci. 2024, 25, 876. [Google Scholar] [CrossRef] [PubMed]
- Garrido, C.; Brunet, M.; Didelot, C.; Zermati, Y.; Schmitt, E.; Kroemer, G. Heat Shock Proteins 27 and 70: Anti-Apoptotic Proteins with Tumorigenic Properties. Cell Cycle 2006, 5, 2592–2601. [Google Scholar] [CrossRef]
- Blank, M.; Mandel, M.; Keisari, Y.; Meruelo, D.; Lavie, G. Enhanced ubiquitinylation of heat shock protein 90 as a potential mechanism for mitotic cell death in cancer cells induced with hypericin. Cancer Res. 2003, 63, 8241–8247. [Google Scholar]
- Wang, S.; Zhang, X.; Wang, H.; Wang, Y.; Chen, P.; Wang, L. Heat Shock Protein 27 Enhances SUMOylation of Heat Shock Protein B8 to Accelerate the Progression of Breast Cancer. Am. J. Pathol. 2020, 190, 2464–2477. [Google Scholar] [CrossRef]
- Miao, J.; Li, L.; Shaheen, N.; Wei, J.; Jacko, A.M.; Sundd, P.; Taleb, S.J.; Mallampalli, R.K.; Zhao, Y.; Zhao, J. The deubiquitinase USP40 preserves endothelial integrity by targeting the heat shock protein HSP90β. Exp. Mol. Med. 2024, 56, 395–407. [Google Scholar] [CrossRef] [PubMed]
Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content. |
© 2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Share and Cite
Gao, R.; Wu, Y.; Wang, Y.; Yang, Z.; Mao, Y.; Yang, Y.; Yang, C.; Chen, Z. Ubiquitination and De-Ubiquitination in the Synthesis of Cow Milk Fat: Reality and Prospects. Molecules 2024, 29, 4093. https://doi.org/10.3390/molecules29174093
Gao R, Wu Y, Wang Y, Yang Z, Mao Y, Yang Y, Yang C, Chen Z. Ubiquitination and De-Ubiquitination in the Synthesis of Cow Milk Fat: Reality and Prospects. Molecules. 2024; 29(17):4093. https://doi.org/10.3390/molecules29174093
Chicago/Turabian StyleGao, Rui, Yanni Wu, Yuhao Wang, Zhangping Yang, Yongjiang Mao, Yi Yang, Chunhua Yang, and Zhi Chen. 2024. "Ubiquitination and De-Ubiquitination in the Synthesis of Cow Milk Fat: Reality and Prospects" Molecules 29, no. 17: 4093. https://doi.org/10.3390/molecules29174093