Regulation of Dual-Specificity Phosphatase (DUSP) Ubiquitination and Protein Stability
Abstract
:1. The DUSP Family Phosphatases
2. Negative Regulation of DUSPs by Lys48-Linked Ubiquitination and Proteasomal Degradation
3. Other Post-Translational Regulations of DUSP Ubiquitination and/or Stability
3.1. Phosphorylation
3.2. Oxidation
3.3. Methylation
4. Dysregulation of DUSPs in Diseases
5. Conclusions
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
Abbreviations
Ub | ubiquitination |
DUSP | dual-specificity phosphatase |
MKP | MAP kinase phosphatase |
MAPK | mitogen-activated protein kinase |
KIM | kinase-interacting motif |
Skp2 | S-phase kinase-associated protein |
Cks1 | cyclin-dependent kinase regulatory subunit 1 |
FoxM1 | forkhead box M1 |
STAT1 | signal transducer and activator of transcription 1 |
LncRNA | long non-coding RNA |
EGF | epidermal growth factor |
PRMT5 | protein arginine methyltransferase 5 |
TFH | T follicular helper cell |
EAE | experimental autoimmune encephalomyelitis |
SLE | systemic lupus erythematosus |
SPOP | Speckle-type POZ protein |
PDGF-BB | platelet-derived growth factor-B chains |
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Classification | Gene Symbol | Alias | Domain Structure | MAPK Substrates | ||
---|---|---|---|---|---|---|
Typical DUSPs (also named MKPs) | DUSP1 | MKP1, CL100, VH1, HVH1, PTPN10 | | JNK, p38 > ERK | ||
DUSP4 | MKP2, VH2, HVH2, TYP | | ERK, JNK > p38 | |||
DUSP6 | MKP3, PYST1 | | ERK | |||
DUSP7 | PYST2, MKPX* | | ERK | |||
DUSP9 | MKP4 | | ERK > p38 | |||
DUSP10 | MKP5 | | JNK, p38 | |||
DUSP16 | MKP7 | | JNK (p38?) | |||
Typical DUSPs (not named as MKPs) | DUSP2 | PAC1 | | ERK, JNK, p38 | ||
DUSP5 | VH3, HVH3 | | ERK | |||
DUSP8 | HB5, VH5, HVH-5, HVH8, (Mouse: M3/6) | | JNK (p38?) | |||
Atypical DUSPs | DUSP3 | VHR | | |||
DUSP11 | PIR1 | | ||||
DUSP12 | YVH1 | | ||||
DUSP13 | DUSP13A, DUSP13B, BEDP, MDSP, SKRP4, TMDP | | ||||
DUSP15 | VHY | | ||||
DUSP18 | DUSP20, LMW-DSP20 | | ||||
DUSP19 | DUSP17, LMW-DSP3, SKRP1, TS-DSP1 | | ||||
DUSP21 | LMW-DSP21 | | ||||
DUSP22 | JKAP, JSP1, VHX, LMW-DSP2, MKPX* | | ||||
DUSP23 | DUSP25, VHZ, LDP-3, MOSP | | ||||
DUSP24 | STYXL1, MK-STYX | | ||||
DUSP27 | | |||||
DUSP28 | VHP, DUSP26# | | ||||
Atypical DUSPs (also named MKPs) | DUSP14 | MKP6, MKP-L | | JNK > ERK > p38 | ||
DUSP26 | MKP8, LDP-4, NATA1, SKRP3, NEAP, DUSP24# | | p38 (ERK?) | |||
| | | | | | |
Cdc25-homology | Kinase-interacting motif (KIM) | Phosphatase | Phosphatase (inactive) | PEST | Disintegrin | Unknown |
Stimuli | Stability | Modification | Modification Enzyme | Experimental Methods | Reference | ||||
---|---|---|---|---|---|---|---|---|---|
Protein Level | Half-Life | Ubiquitination | Proteasome Inhibitor | ||||||
DUSP1 | Serum | ↓ | Phosphorylation↑ (human Ser296 †/Ser323 †); Ubiquitination↑ | ERK; CUL1 | ✓ | ✓ | ✓ | LLnL; MG132 | [28,54] |
Estradiol | ↑ | Phosphorylation↑ (human Ser359 †/Ser364 †) | ERK | ✓ | ✓ | ✓ | LLnL; MG132; Lactacystin | [56] | |
LPS | ↑ | Phosphorylation↑ (human Ser359 †/Ser364 †) | ERK | ✓ | ✓ | ? | MG132; PS-341 | [57] | |
Pb2+ | ↓ | Ubiquitination↑ | ✓ | ✓ | ✓ | LLnL; MG132 | [27] | ||
Glutamate/ PKCδ | ↓ | Ubiquitination↑ | ✓ | ✓ | MG132; LLnL; Lactacystin | [31] | |||
Atrogin-1 upregulation | ↓ | Ubiquitination↑ | Atrogin-1 | ✓ | ✓ | ✓ | MG132 | [33] | |
USP49 upregulation | ↑ | Ubiquitination↓ | USP49 | ✓ | ✓ | MG132 | [34] | ||
KLF5 upregulation | ↑ | Phosphorylation↑ (human Ser359 †/Ser364 †) | ERK | ✓ | ✓ | MG132 | [58] | ||
LPS | ↑ | Phosphorylation↑ (human Ser359 †/Ser364 †) | ERK | ✓ | ✓ | [59] | |||
Insulin | ↑ | Phosphorylation↑ | ✓ | MG132; Lactacystin | [63] | ||||
Asbestos/ ROS | ↓ | Oxidation↑ | ✓ | MG132 | [82] | ||||
TNFα/ ROS | ↓ | Oxidation↑ | ✓ | MG132 | [79] | ||||
ROS | ↓ | S-glutathionylation↑ (human Cys258 †) | ✓ | MG132 | [81] | ||||
Glucocorticoid | ↑ | ✓ | MG132; LLnL | [60] | |||||
EGF plus Lactoferrin | ↓ | ✓ | MG132 | [32] | |||||
Angiotensin II/ PKA | ↓ | ✓ | Bortezomib | [35] | |||||
CaMKII inhibition | ↓ | ✓ | MG132 | [64] | |||||
Luteolin/ Superoxide | ↓ | ✓ | ✓ | MG132 | [80] | ||||
DUSP2 | ERK4 | ↑ | ✓ | ✓ | [65] | ||||
DUSP4 | LPS | ↑ | Phosphorylation↑ (human Ser386 †/Ser391 †) | ERK | ✓ | ✓ | ? | MG132; PS-341 | [57] |
ERK inhibitor | ↓ | Phosphorylation↓ (human Ser386 †/Ser391 †); Ubiquitination↑ | ERK | ✓ | ✓ | ✓ | MG132 | [67] | |
Cd2+ / Oxidative stress | ↓ | Oxidation↑ | GSSG | ✓ | [83] | ||||
8-Bromo-cAMP | ↑ | ✓ | ✓ | MG132 | [38] | ||||
Senescence | ↑ | ✓ | ✓ | MG132 | [37] | ||||
DUSP5 | ERK2 binding | ↑ | Ubiquitination↓ | ✓ | ✓ | ✓ | MG132 | [39] | |
DUSP6 | Serum | ↓ | Phosphorylation↑ (human Ser159 †/Ser197 †) Ubiquitination↑ | ERK | ✓ | ✓ | ✓ | LLnL; Lactacystin | [70,73] |
ROS | ↓ | Phosphorylation↑ (human Ser159 †/Ser197 †); Ubiquitination↑ | ✓ | ✓ | MG132 | [43] | |||
PDGF | ↓ | Phosphorylation↑ (human Ser174 †); Ubiquitination↑ | ✓ | ✓ | ✓ | MG132 | [74] | ||
P2X7 nucleotide, EGF | ↓ | Phosphorylation↑ (human Ser197 †) | ERK | ✓ | ✓ | MG132 | [71] | ||
Insulin | ↓ | Phosphorylation↑ (human Ser159 †/Ser197 †) | ERK | ✓ | ✓ | [72] | |||
Amino acid, insulin, IGF-1/ mTOR | ↓ | Phosphorylation↑ (human Ser159 †) | ✓ | ✓ | [73] | ||||
PKCδ downregulation | ↓ | ✓ | MG132 | [46] | |||||
TSH | ↑ | ✓ | ✓ | MG132 | [44] | ||||
Metformin/ AMP-activated protein kinase | ↓ | ✓ | MG132 | [45] | |||||
EGF plus Lactoferrin | ↓ | ✓ | MG132 | [32] | |||||
DUSP7 | Hypoxic stress/ HIFs | ↓ | Ubiquitination↑ | SPOP | ✓ | ✓ | MG132 | [47] | |
DUSP8 | Anisomycin | ↓ | Phosphorylation↑; Ubiquitination↑ | JNK | ✓ | ✓ | ? | Lactacystin | [52] |
DUSP9 | LincU upregulation | ↑ | Ubiquitination↓ | ✓ | ✓ | ✓ | MG132 | [53] | |
DUSP10 | Insulin | ↑ | Phosphorylation↑ (human Ser224 †/Ser230 †) | mTORC2 | ✓ | ✓ | [75] | ||
DUSP14 | TCR signaling | (Activity↑) | Methylation↑ (human Arg17 †/Arg38 †/Arg45); Ubiquitination↑ (human Lys103 †) | PRMT5; TRAF2 | ✓ | ✓ | [86,87] | ||
DUSP16 | ERK upregulation | ↑ | Phosphorylation↑ (human Ser446 †); Ubiquitination↓ | ERK | ✓ | ✓ | ✓ | MG132; MG115 | [77,78] |
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Chen, H.-F.; Chuang, H.-C.; Tan, T.-H. Regulation of Dual-Specificity Phosphatase (DUSP) Ubiquitination and Protein Stability. Int. J. Mol. Sci. 2019, 20, 2668. https://doi.org/10.3390/ijms20112668
Chen H-F, Chuang H-C, Tan T-H. Regulation of Dual-Specificity Phosphatase (DUSP) Ubiquitination and Protein Stability. International Journal of Molecular Sciences. 2019; 20(11):2668. https://doi.org/10.3390/ijms20112668
Chicago/Turabian StyleChen, Hsueh-Fen, Huai-Chia Chuang, and Tse-Hua Tan. 2019. "Regulation of Dual-Specificity Phosphatase (DUSP) Ubiquitination and Protein Stability" International Journal of Molecular Sciences 20, no. 11: 2668. https://doi.org/10.3390/ijms20112668