| First Author | Zou Q | Year | 2014 |
| Journal | Nat Immunol | Volume | 15 |
| Issue | 6 | Pages | 562-70 |
| PubMed ID | 24777531 | Mgi Jnum | J:259597 |
| Mgi Id | MGI:6142028 | Doi | 10.1038/ni.2885 |
| Citation | Zou Q, et al. (2014) USP15 stabilizes MDM2 to mediate cancer-cell survival and inhibit antitumor T cell responses. Nat Immunol 15(6):562-70 |
| abstractText | Deubiquitinases (DUBs) are a new class of drug targets, although the physiological function of only few DUBs has been characterized. Here we identified the DUB USP15 as a crucial negative regulator of T cell activation. USP15 stabilized the E3 ubiquitin ligase MDM2, which in turn negatively regulated T cell activation by targeting the degradation of the transcription factor NFATc2. USP15 deficiency promoted T cell activation in vitro and enhanced T cell responses to bacterial infection and tumor challenge in vivo. USP15 also stabilized MDM2 in cancer cells and regulated p53 function and cancer-cell survival. Our results suggest that inhibition of USP15 may both induce tumor cell apoptosis and boost antitumor T cell responses. |
