Table 1.
List of DUBs Regulating Cell Cycle
| Name | Family/Domains | Cell Cycle Stage | Function | Substrate(s) | References |
|---|---|---|---|---|---|
| USP13 | USP/ZnF-UBP, UBA, USP | G1 | Together with Ufd1, couples the endoplasmic reticulum stress response to cell cycle control | Skp2 | 129 |
| BAP1 | UCH/UCH, coiled coil | G1/S | Promotes cell cycle progression by interacting with HCF-1, a transcriptional cofactor for genes required for S phase | HCF-1 | 130 |
| USP1 | USP/USP | S | Switches off DNA damage pathways, limits the error-prone replication in absence or presence of extrinsic DNA damage | FANCD2-FANCI, PCNA | 131 -134 |
| USP3 | USP/ZnF-UBP, USP | S | Necessary for proper progression through S phase, involved in DNA damage response and prevents replicative stress | H2A (major substrate), H2B | 135 |
| BRCC36 | JAMM/JAMM, coiled coil | DNA damage checkpoint | Allows the turnover of BRCA1-mediated repair in DNA damage response | H2A, H2AX | 136, 137 |
| OTUB1 | OTU/OTU | DNA damage checkpoint | Noncanonical inhibition of DNA damage response (by blocking ubiquitin transfer) | UBC13 (interacting protein) | 67, 138 |
| USP28 | USP/UBA, UIM, USP, coiled coil | DNA damage checkpoint | Regulates the stability of DNA-damage signaling factors, controls stability of c-Myc | Chk2, 53BP1, Claspin, c-Myc | 139, 140 |
| USP7 | USP/MATH, USP, UBL | G1/S and G2/M | Regulates the p53-MDM2 pathway | MDM2, p53 | 141, 142 |
| USP37 | USP/UIM, USP | G1/S, G2/M | Promotes the G1/S transition by inhibiting the APC/C-dependent degradation of Cyclin A, regulation of unknown substrate necessary for the prevention of mitotic entry | Cyclin A, itself, other unknown substrate | 79, 84 |
| USP42 | USP/USP | G1/S and G2/M | Necessary for early activation of p53 response | p53 | 143 |
| USP2a | USP/USP | G1/S and G2/M | Regulates the p53-MDM2 pathway | MDM2 | 144 |
| USP50 | USP/USP (predicted to be inactive) | G2/M | Regulates the HSP90-dependent stability of Wee1 (unknown mechanism) | Not known | 145 |
| CYLD | USP/CAP-Gly domains, USP with B-box | M, G1/S | Regulates mitotic entry, assembly of the mitotic spindle, cytokinesis rate after TPA treatment, negatively regulates G1/S progression after TPA treatment | PLK1 (?), Bcl3 | 43, 58, 59 |
| USP16 | USP/ZnF-UBP, USP | M | Necessary for M phase progression, associated with reversal of DNA silencing after DNA damage response | H2A | 146, 147 |
| USP44 | USP/ZnF-UBP, USP | M | Regulation of spindle assembly checkpoint (SAC) | CDC20 | 36, 37 |
| USP4 | USP/DUSP, UBL, USP | M | Regulation of spindle assembly checkpoint (SAC) | Splicing of a-tubulin and Bub1 mRNA, other mRNAs important for SAC (?) | 70 |
| USP39 | USP/ZnF-UBP, USP (inactive) | M | Regulation of spindle assembly checkpoint (SAC) | Splicing of Aurora B mRNA, other mRNAs important for SAC (?) | 62 |
| USP9x | USP/UBL, USP | M | Regulation of chromosome alignment and segregation by controlling the dynamic dissociation of Survivin from centromeres | Survivin | 125 |
| UBPY | USP, MIT, Rhodanese, USP | M | Deubiquitination of proteins (including VAMP8) during cytokinesis | VAMP8, other substrates | 148 |
| AMSH | JAMM/MPN+, MIT | M | Deubiquitination of proteins (including VAMP8) during cytokinesis | VAMP8, other substrates | 148 |
The table depicts DUBs known to be involved in cell cycle progression at different cell cycle stages (S [S phase], G1, G2, and M [mitosis]) and transitions. The role and regulation of mitotic DUBs are described in detail in the text. The domain composition and specific substrates of the DUBs are depicted.
?
indicates unconfirmed speculation.