Post-translational control of beige fat biogenesis by PRDM16 stabilization.

ABSTRACT: Compelling evidence shows that brown and beige adipose tissue are protective against metabolic diseases^1,2. PR domain-containing 16 (PRDM16) is a dominant activator of the biogenesis of beige adipocytes by forming a complex with transcriptional and epigenetic factors and is therefore an attractive target for improving metabolic health^3-8. However, a lack of knowledge surrounding the regulation of PRDM16 protein expression hampered us from selectively targeting this transcriptional pathway. Here we identify CUL2-APPBP2 as the ubiquitin E3 ligase that determines PRDM16 protein stability by catalysing its polyubiquitination. Inhibition of CUL2-APPBP2 sufficiently extended the half-life of PRDM16 protein and promoted beige adipocyte biogenesis. By contrast, elevated CUL2-

SUBMITTER: Wang Q 

PROVIDER: S-EPMC9433319 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature