Table 1.
The list of DUBs and cellular substrates involved in the Warburg effect.
| DUBs | Substrates | Functions | References |
|---|---|---|---|
| USP7 | SIRT7 | USP7 decreases the K-63 linked ubiquitination level of SIRT7. | [78] |
| USP7 decreases the ubiquitin level of SIRT7 as the glucose concentration increased. | |||
| G6PC | Deubiquitination of SIRT7 by USP7 inhibits the expression of G6PC, a key regulator of SIRT7-mediated glucose production. | ||
| FoxO1 | USP7 deubiquitinates and regulates FoxO1 occupancy in the promoter of the glucose-generating gene. | [82] | |
| USP19 | HIF-1α | Silence of USP19 decreased the protein level of HIF-1α. | [92] |
| VEGF | Silence of USP19 decreased the mRNA level of VEGF. | ||
| GLUT1 | Silence of USP19 decreased the mRNA level of GLUT1. | ||
| USP28 | c-Myc | USP28 deubiquitinates c-Myc through interaction with Fbw7. | [97] |
| USP37 | c-Myc | USP37 directly binds to c-Myc and deubiquitinates the c-Myc. | [104] |
| GLUT1 | Depletion of USP37 leads to decreased expression of GLUT1 mRNAs required for glucose uptake. | ||
| LDHA | Depletion of USP37 leads to decreased expression of LDHA mRNAs required for lactic acid production. | ||
| USP44 | FBP1 | Knockdown of USP44 improves glucose utilization and lactic acid production capacity by reducing FBP1. | [114] |
| OTUB2 | c-Myc | OTUB2 increases the expression level of c-Myc. | [119] |
| HIF-1α | OTUB2 increases the expression level of HIF-1α. | ||
| GLUT1 | OTUB2 increases the expression level of GLUT1. | ||
| U2AF2 | OTUB2 increases the expression level of U2AF2. | ||
| OTUB2 regulates the Warburg effect via interaction with U2AF2. | |||
| HK2 | OTUB2 increases the expression level of HK2. | ||
| PGAM1 | OTUB2 increases the expression level of PGAM1. | ||
| PGK1 | OTUB2 increases the expression level of PGK1. | ||
| mTOR | OTUB2 increases the level of phosphorylation of mTOR. | ||
| AKT | OTUB2 increases the level of phosphorylation of AKT. | ||
| OTUD6B | HIF-1α | Overexpression of OTUD6B increased the ubiquitination level of HIF-1α and decreased protein level of HIF-1α. | [126,127] |
| pVHL | OTUD6B inhibits pVHL from proteasome degradation through binding with elongin B and enhancing the interaction with pVHL-elongin C. | ||
| OTUD7B | HIF-1α | Knockdown of OTUD7B decreases the protein levels of HIF-1α and increases the K11-linked polyubiquitin chain. | [133] |