UBE2M is a stress-inducible dual E2 for neddylation and ubiquitylation that promotes targeted degradation of UBE2F. Weihua Zhou et al
| Main Author: | Sun, Yi |
|---|---|
| Other Authors: | Zhou, Weihua, Xu, Jie, Tan, Mingjia, Zhang, Jinfang, Li, Haomin, Li, Hua, Wei, Wenyi |
| Format: | Dataset |
| Terbitan: |
Mendeley
, 2018
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| Subjects: | |
| Online Access: |
https:/data.mendeley.com/datasets/g3xxjdhwkt |
Daftar Isi:
- UBE2M and UBE2F are two family members of neddylation E2 conjugating enzyme that, together with E3s, activate CRLs (Cullin-RING Ligases) by catalyzing cullin neddylation. However, whether and how two E2s cross-talk with each other are largely unknown. Here, we report that UBE2M is a stress-inducible gene subjected to cis-transactivation by HIF-1α and AP1, and MLN4924, a small molecule inhibitor of E1 NEDD8-activating enzyme (NAE), up-regulates UBE2M via blocking degradation of HIF-1α and AP1. UBE2M is a dual E2 for targeted ubiquitylation and degradation of UBE2F, acting as a neddylation E2 to activate CUL3-Keap1 E3 under physiological condition, but as an ubiquitylation E2 for Parkin-DJ-1 E3 under stressed conditions. UBE2M-induced UBE2F degradation leads to CRL5 inactivation and subsequent NOXA accumulation to suppress the growth of lung cancer cells. Collectively, our study establishes a negative regulatory axis between two neddylation E2s with UBE2M ubiquitylating UBE2F, and two CRLs with CRL3 inactivating CRL5.