Ubiquitination Links DNA Damage and Repair Signaling to Cancer Metabolism
Abstract
:1. Introduction
2. The Effects of Ubiquitination on Cancer Metabolism
3. The Effects of Ubiquitination on DNA Damage and DNA Repair
4. E3 Ligase Involved in Cancer Metabolism and DNA Damage
4.1. NEDD4
4.2. APC/CCDH1
4.3. FBXW7
4.4. Pellino1
5. Current Therapeutic Implications in Cancer Targeting Ubiquitination
6. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Name | Type | Substrate | Ubiquitination Residue | Cancer Type | Ref. (PMID Number) |
---|---|---|---|---|---|
E4F1 | atypical | p53 | K48 | osteosarcoma, hepatocellular carcinoma | 17110336, 24163401 |
HectH9 | HECT | c-Myc | K63 | retinoblastoma | 31677785 |
HUWE1 | HECT | HAUSP | K63 | lung cancer, prostatic adenocarcinoma | 30176860, 27934968 |
c-Myc | K48, K63 | breast cancer | 30176860 | ||
p53 | K48 | B cell lymphoma | 30176860 | ||
WIPI2 | unknown | pancreatic cancer | 30340022, 34502089 | ||
HK2 | K63 | prostate cancer | 31201299 | ||
NEDD4 | HECT | AKT | K63, K48 | breast cancer, hepatocellular carcinoma | 23195959, 31390487 |
PTEN | K63 | prostate cancer | 17218261, 17218260 | ||
Beclin-1 | K11 | adenocarcinoma | 21936852 | ||
NEDD4L | HECT | ULK1 | K27, K29 | adenocarcinoma | 27932573 |
UBR5 | HECT | citrate synthase (CS) | unknown | breast cancer | 30850587 |
WWP1 | HECT | PTEN | K27 | prostate cancer | 31097636 |
WWP2 | HECT | PTEN | unknown | prostate cancer | 21532586 |
PARKIN | RBR | mTOR | unknown | ganglioglioma | 28803490 |
HIF-1α | unknown | breast cancer | 29180628 | ||
PKM2 | unknown | lung cancer, glioblastoma | 26975375 | ||
PHGDH | unknown | breast cancer, lung cancer | 32478681 | ||
APC/CCDH1 | multimeric RING | PFKFB3 | unknown | neuroblastoma, adenocarcinoma | 20080744, 24604252, 21402913 |
PAH | K48, K63 (no direct evidence) | hepatocellular carcinoma | 33260674 | ||
GLS1 | unknown | colorectal cancer | 27902968 | ||
IDH3β | unknown | esophageal squamous cell carcinoma | 31053633 | ||
BRCA1 | RING | AKT | K48 | breast cancer | 19074868 |
CARP1/2 | RING | p53 | K48 | lung cancer, colorectal cancer | 17121812 |
COP1 | RING | p53 | K48 | osteosarcoma | 15103385 |
FASN | unknown | adenocarcinoma | 23269672 | ||
CRL4A | RING | AMPKα | K29, K63 | ovarian cancer | 30807229 |
CUL3-KLHL20 | RING | ULK1 | K48 | adenocarcinoma | 26687681 |
CUL3-KLHL22 | RING | DEPDC5 | K48 | breast cancer | 29769719 |
CUL3-KLHL25 | RING | ACLY | unknown | lung cancer | 27664236 |
CUL3-SPOP | RING | PrLZ | K48 | prostate cancer | 35194188 |
CUL4-DDB1 | RING | Raptor | K63 | lung cancer | 18235224 |
CUL4-DDB1 (AMBRA1) | RING | Beclin-1 | K63 | colon cancer, pancreatic ductal adenocacinoma | 27308402, 23974797 |
CUL5 | RING | p53 | K48 | B-cell chronic lymphocytic leukemia | 17449237, 32194910 |
CUL7 | RING | p53 | unknown | lung cancer, breast cancer | 17942889, 25003318 |
GID | RING | AMPK | K48 | adenocarcinoma, osteosarcoma | 31795790, 25679763 |
Gp78 | RING | HMGCR | unknown | breast cancer, prostate cancer | 22143767, 33718197 |
MAGE-TRIM28 | RING | FBP1 | unknown | hepatocellular carcinoma | 28394358 |
MDM2 | RING | p53 | K48 | breast cancer | 9153396, 34650049 |
MDM2 | RING | PGAM | unknown | lung cancer | 24567357 |
MKRN1 | RING | p53 | K48 | lung cancer, colon cancer | 19536131, 20930521 |
MULAN | RING | AKT | K48 | adenocarcinoma | 22410793 |
Pirh2 | RING | p53 | K48 | osteosarcoma | 12654245 |
RFP | RING | PTEN | K48 | plasmacytoma, myeloma, endometrial cancer, colon carcinoma | 23419514 |
RING1 | RING | p53 | K48 | liver cancer | 29187402 |
RNF2 | RING | AMBRA1 | K48 | thymus lymphoma | 24980959, 28789945 |
RNF5 | RING | SLC1A5/ SLC38A2 | unknown | breast cancer | 25759021 |
RNF8 | RING | histone H3 | K48 | breast cancer, epidermoid carcinoma | 28507061 |
RNF115 | RING | p53 | unknown | lung adenocarcinoma | 32553631 |
RNF126 | RING | mTOR | K48 | acute myeloid leukemia | 32131492 |
PDK | unknown | breast cancer | 27462466 | ||
RNF139 | RING | SREBP1 precursor | unknown | renal cell carcinoma | 20068067 |
RNF145 | RING | HMGCR | unknown | adenocarcinoma, hepatocellular carcinoma | 29374057, 30543180 |
RNF152 | RING | RagA | K63 | non-small cell lung cancer | 25936802, 32486221 |
Rheb | unknown | colon cancer | 30514904, 32486221 | ||
RNF216 | RING | Beclin-1 | K48 | adenocarcinoma | 29361549 |
SCFFBXL6 | RING | HSP90AA1 | K63 | hepatocellular carcinoma | 32576198 |
SCFFBXL8 | RING | mTOR | K48 | colorectal carcinoma | 27916606 |
SCFFBXL14 | RING | c-Myc | K48? | glioma | 27923907 |
SCFFBXL18 | RING | AKT | K63 | glioma | 27926990 |
SCFFBXL20 | RING | VPS34 | unknown | adenocarcinoma, glioma | 25593308 |
SCFFBXO32 | RING | c-Myc | K48 | ovary cancer | 25944903 |
SCFFBXW7 | RING | SREBP1 | unknown | glioma | 34737211, 36176395 |
mTOR | K48 | breast cancer | 30086763, 18787170 | ||
HIF-1α | K48 | ovarian cancer | 21964756 | ||
c-Myc | K48 | T-acute lymphoblastic leukemia, uterine cancer, colorectal cancer, bladder cancer, lung cancer | 30086763, 33260160, 23750012, 20852628, 28665315 | ||
p53 | K48 | adenocarcinoma, colorectal cancer | 31905981, 25314076 | ||
SCFSKP2 | RING | c-Myc | K48 | B cell lymphoma | 12769844, 12769843, 28665315 |
AKT | K63 | breast cancer | 22632973 | ||
RagA | K63 | adenocarcinoma | 26051179 | ||
SCFβ-TrCP | RING | DEPTOR | unknown | breast cancer, ovarian cancer | 22017876, 22454292 |
Myc | K33, K48, K63 | osteosarcoma | 20852628 | ||
PFKFB3 | unknown | adenocarcinoma | 21402913 | ||
NRF2 | unknown | endometrioid carcinoma | 25937177 | ||
SIAH2 | RING | α-KGDHC | unknown | adenocarcinoma, tongue cancer, renal cancer | 15466852, 24506869 |
Synoviolin | RING | p53 | K48 | colon cancer | 25128494, 20930521, 17170702 |
TOPORS | RING | HIF-1α | K63 | colon cancer | 23722539 |
TRAF2 | RING | mLST8 | K63 | ovarian cancer, melanoma, adenocarcinoma | 28489822 |
TRAF4 | RING | AKT | K63 | lung cancer | 24154876 |
TRAF6 | RING | p62 | K63 | prostate cancer, lung cancer | 23911927 |
AKT | K63 | prostate cancer | 19713527 | ||
HIF-1α | K63 | colon cancer, adenocarcinoma | 23722539 | ||
ULK1 | K63 | chronic myeloid leukemia | 30929559 | ||
Beclin-1 | K63 | leukemia | 20501938 | ||
HK2 | K63 | liver cancer | 28980855 | ||
TRC8/RNF139 | RING | HMGCR | unknown | renal cell carcinoma | 20068067 |
TRIM16 | RING | NRF2 | K63 | adenocarcinoma | 30525100 |
ULK1 | K63 | acute monocytic leukemia | 27693506 | ||
TRIM21 | RING | PFKP | K48 | glioma | 29038421 |
TRIM25 | RING | PTEN | K63 | lung cancer | 33931764 |
TRIM31 | RING | TSC1-TSC2 | K48 | hepatocellular carcinoma | 28967907 |
p53 | K48 | breast cancer | 34650049 | ||
TRIM32 | RING | ULK1 | K63 | colon cancer, lung cancer, hepatocellular carcinoma | 31123703 |
TRIM45 | RING | p53 | K48 | glioma | 28542145 |
TRIM50 | RING | Beclin-1 | K63 | adenocarcinoma | 29604308 |
TTC3 | RING | AKT | K48 | B Cell Lymphoma | 20059950 |
VHL | RING | HIF-1α | K48 | adenocarcinoma | 25958982, 12086861 |
XIAP | RING | HIF-1α | K63 | osteosarcoma, renal cell carcinoma | 28666324 |
ZNRF1 | RING | AKT | K48 | neuroblastoma | 22057101 |
Peli1 | RING-like | PKC theta | K48 | T cell lymphoma, colon adenocarcinoma | 35058288 |
TSC1 | K63 | melanoma | 33215753 | ||
CHIP | U-box | AKT | K48 | breast cancer, adenocarcinoma | 21767636 |
p53 | K48 | lung cancer, colon cancer | 29953728 |
Name | Type | Substrate | Ubiquitination Residue | Ref. (PMID Number) |
---|---|---|---|---|
ARF-BP1/Mule | HECT | p53 | unknown | 15989956 |
MCL-1 | unknown | 15989957 | ||
E6-AP | HECT | p53 | unknown | 31749782 |
HUWE1 | HECT | histone H1 | unknown | 29127375 |
ITCH | HECT | p73 | unknown | 15678106 |
p63 | unknown | 16908849 | ||
WWOX | K63 | 25331887 | ||
H1.2 | K48, K63 | 30517763 | ||
NEDD4 | HECT | RNA PolⅡ | unknown | 17996703 |
Mdm2 | K63 | 24413081 | ||
NEDD4L | HECT | OGG1 | unknown | 33282879 |
Rsp5 | HECT | RNA PolⅡ | unknown | 9108033 |
Smurf1 | HECT | RhoB | unknown | 25249323 |
Smurf2 | HECT | H2AX | unknown | 31533041 |
RNF20 | unknown | 33097595 | ||
TRIP12 | HECT | USP7/HAUSP | K48 | 27800609 |
UBR5 | HECT | ATMIN | unknown | 25092319 |
WWP2 | HECT | SOX2 | unknown | 25042802, 34193614 |
APC/CCdc20 | multimeric RING | MCL-1 | unknown | 29987118 |
BIM | unknown | 24871945 | ||
APC/CCDH1 | multimeric RING | CtIP | unknown | 25349192 |
E2F1 | K11 | 22580462 | ||
BRCA1 | RING | CtIP | unknown | 16818604 |
BRCA1-BARD1 | RING | histone H2A | mono | 33589814 |
RNA PolⅡ | K6 | 15886201, 15905410 | ||
CHFR | RING | PARP1 | K48, K63 | 23268447 |
COP1 | RING | p53 | unknown | 16931761 |
CRL4ADDB1 | RING | p53 | unknown | 17967871 |
p73 | unknown | 23085759 | ||
CRL4Cdt2 | RING | p21 | unknown | 18794347 |
Cul4B | RING | p53 | K48 (no direct evidence) | 33524014 |
HUWE1 | unknown | 25883150 | ||
CUL4-DDB-ROC1 | RING | histone H3, H4 | unknown | 16678110 |
FANCL | RING | FANCD2 | unknown | 17352736 |
MARCH7 | RING | Mdm2 | K63 | 29295817 |
Mdm2 | RING | p53 | K48 | 12507556 |
p73 | unknown | 34716260 | ||
Pirh2 | RING | p53 | K48 | 12654245 |
CHK2 | unknown | 23449389 | ||
p73 | K11, K29, K48, K63 | 21994467 | ||
Rad5 | RING | PCNA | K63 | 18757916 |
Rad6 | RING | PCNA | K63 | 12226657 |
Rad18 | RING | PCNA | K63 | 19851286 |
RFWD3-Mdm2 | RING | p53 | unknown | 20173098 |
RNF2 | RING | H2AX | unknown | 21676867 |
RNF8 | RING | MDC1 | K63 | 18006705, 31182912 |
histone H1 | K63 | 29127375 | ||
histone H2A, H2AX | K63 | 22980979 | ||
JMJD2A | K48 | 22373579 | ||
Ku80 | K48 | 22266820 | ||
PCNA | unknown | 18948756 | ||
NBS1 | unknown | 23115235 | ||
RecQL4 | K6, K27, K29 | 33674555 | ||
RNF19A | RING | BARD1 | K63 | 34789768 |
RNF20/RNF40 | RING | histone H2B | unknown | 30692271 |
RNF111 | RING | XPC | unknown | 23751493 |
RNF168 | RING | histone H2A | K27, K63 | 25578731, 22980979 |
JMJD2A | unknown | 22373579 | ||
H2AX | unknown | 31533041 | ||
SCFFBXW7 | RING | p53 | K48 | 31346036, 31337255 |
p63 | unknown | 20571051 | ||
XRCC4 | K63 | 26774286 | ||
PLK1 | K48 | 24970797 | ||
SOX9 | unknown | 27566146 | ||
BLM | K48 | 26028025 | ||
SCFSKP2 | RING | NBS1 | K63 | 22464731 |
SCFβ-TrCP | RING | BIM | unknown | 19150432 |
CDC25A | unknown | 14681206 | ||
CLASPIN | unknown | 16885022 | ||
SCFβ-TrCP1 | RING | Mdm2 | K48 | 33676897 |
SCFβ-TrCP2 | RING | Mdm2 | K63 | 33676897 |
TRIM17 | RING | MCL-1 | unknown | 22976837 |
TRIM24 | RING | p53 | unknown | 24820418 |
UHRF1 | RING | RIF1 | K63 | 26727879 |
Peli1 | RING-like | NBS1 | K63 | 30952868 |
PRP19 | U-box | RPA | K63 | 24332808 |
Target | Compounds | Chemical Formula |
---|---|---|
20S Proteasome | Bortezomib | C19H25BN4O4 |
Carfilzomib | C40H57N5O7 | |
Oprozomib | C25H32N4O7S | |
Ixazomib | C14H19BCl2N2O4 | |
E1 enzyme | TAK-243 (MLN7243) | C19H20F3N5O5S2 |
E2 enzyme | CC0651 | C20H21Cl2NO6 |
NSC697923 | C11H9NO5S | |
Leucettamol A | C30H52N2O2 | |
Manadosterol A | C54H83Na5O21S5 | |
Manadosterol B | C54H84Na4O18S4 | |
E3 ligase | Nutlin-3a | C30H30Cl2N4O4 |
KRT-232 (AMG 232) | C28H35Cl2NO5S | |
Milademetan (DS-3032) | C30H34Cl2FN5O4 | |
HDM201 | C26H24Cl2N6O4 | |
ALRN-6924 | C95H140N20O23 | |
GDC-0917 | C29H36N6O4S | |
Debio1143 (Xevinapant) | C32H43N5O4 | |
Apcin | C13H14Cl3N7O4 | |
TAME | C14H22N4O4S | |
Oridonin | C20H28O6 | |
SZL-P1-41 | C24H24N2O3S | |
Longikaurin A | C20H28O5 | |
Curcumin | C21H20O6 | |
Dioscin | C45H72O16 | |
GS143 | C28H19FN2O4 | |
Erioflorin | C19H24O6 | |
Deubiquitinase (DUB) | IU1 | C18H21FN2O |
IU1-47 | C19H23ClN2O | |
WP1130 | C19H18BrN3O | |
HBX 41,108 | C13H3ClN4O |
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Koo, S.-Y.; Park, E.-J.; Noh, H.-J.; Jo, S.-M.; Ko, B.-K.; Shin, H.-J.; Lee, C.-W. Ubiquitination Links DNA Damage and Repair Signaling to Cancer Metabolism. Int. J. Mol. Sci. 2023, 24, 8441. https://doi.org/10.3390/ijms24098441
Koo S-Y, Park E-J, Noh H-J, Jo S-M, Ko B-K, Shin H-J, Lee C-W. Ubiquitination Links DNA Damage and Repair Signaling to Cancer Metabolism. International Journal of Molecular Sciences. 2023; 24(9):8441. https://doi.org/10.3390/ijms24098441
Chicago/Turabian StyleKoo, Seo-Young, Eun-Ji Park, Hyun-Ji Noh, Su-Mi Jo, Bo-Kyoung Ko, Hyun-Jin Shin, and Chang-Woo Lee. 2023. "Ubiquitination Links DNA Damage and Repair Signaling to Cancer Metabolism" International Journal of Molecular Sciences 24, no. 9: 8441. https://doi.org/10.3390/ijms24098441