The AMBRA1 E3 ligase adaptor regulates the stability of cyclin D.

ABSTRACT: The initiation of cell division integrates a large number of intra- and extracellular inputs. D-type cyclins (hereafter, cyclin D) couple these inputs to the initiation of DNA replication¹. Increased levels of cyclin D promote cell division by activating cyclin-dependent kinases 4 and 6 (hereafter, CDK4/6), which in turn phosphorylate and inactivate the retinoblastoma tumour suppressor. Accordingly, increased levels and activity of cyclin D-CDK4/6 complexes are strongly linked to unchecked cell proliferation and cancer^2,3. However, the mechanisms that regulate levels of cyclin D are incompletely understood^4,5. Here we show that autophagy and beclin 1 regulator 1 (AMBRA1) is the main regulator of the degradation of cyclin D. We identified AMBRA1 in a genome-

SUBMITTER: Chaikovsky AC 

PROVIDER: S-EPMC8246597 | biostudies-literature | 2021 Apr

REPOSITORIES: biostudies-literature