The Long-Lost Ligase: CRL4AMBRA1 Regulates the Stability of D-Type Cyclins

• DOI: 10.1089/dna.2021.0659
• Publication Date: 2021-09-08T18:39:02Z
• Authors: Andrea C. Chaikovsky; Julien Sage; Michele Pagano; Daniele Simoneschi
• Keywords: Cyclin A; Cyclin E; Cyclin A2; Cyclin D; Cyclin B

D-type cyclins (cyclin D1, D2, and D3, together cyclin D) are central drivers of the cell division cycle well-described proto-oncoproteins. Rapid turnover D is critical for its regulation, but underlying mechanism has remained a matter debate. Recently, AMBRA1 was identified as major regulator stability all three cyclins. serves substrate receptor one ∼40 CUL4-RING E3 ubiquitin ligase (CRL4) complexes to mediate polyubiquitylation subsequent degradation D. Consequently, regulates proliferation impact tumor growth cellular response cycle-targeted cancer therapies. Here we discuss findings that implicate core member machinery.