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. 2023 Jan 23;9:23. doi: 10.1038/s41420-023-01337-w

Fig. 2. UBE2M acts as a dual E2 for neddylation and ubiquitylation to degrade UBE2F.

Fig. 2

Under physiological conditions, UBE2M serves as a neddylation E2 to promote CUL3 neddylation, triggering polyubiquitylation and degradation of UBE2F through CUL3-KEAP1 E3 ligase. Under stressed conditions, UBE2M is transcriptionally activated by HIF-1α or AP-1, which makes it serve as a ubiquitylation E2 to complex with DJ-1/Parkin to promote the ubiquitylation and degradation of UBE2F. Ultimately, the degradation of UBE2F is accompanied by the inactivation of CRL5. TPA: a typical tumor promoter and mitogen stimulator, inducing c-JUN.