Open AccessThe Long-Lost Ligase: CRL4AMBRA1 Regulates the Stability of D-Type Cyclins
Author(s) -
Andrea C. Chaikovsky,
Julien Sage,
Michele Pagano,
Daniele Simoneschi
Publication year - 2021
Publication title -
dna and cell biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.895
H-Index - 77
eISSN - 1557-7430
pISSN - 1044-5498
DOI - 10.1089/dna.2021.0659
Subject(s) - biology , ubiquitin ligase , cyclin a , cyclin , cyclin e , cell cycle , microbiology and biotechnology , cyclin a2 , cyclin d1 , cyclin d , cancer research , cyclin b , cell cycle protein , cell growth , ubiquitin , cell , genetics , gene
D-type cyclins (cyclin D1, D2, and D3, together cyclin D) are central drivers of the cell division cycle and well-described proto-oncoproteins. Rapid turnover of cyclin D is critical for its regulation, but the underlying mechanism has remained a matter of debate. Recently, AMBRA1 was identified as the major regulator of the stability of all three D-type cyclins. AMBRA1 serves as the substrate receptor for one of ∼40 CUL4-RING E3 ubiquitin ligase (CRL4) complexes to mediate the polyubiquitylation and subsequent degradation of cyclin D. Consequently, AMBRA1 regulates cell proliferation to impact tumor growth and the cellular response to cell cycle-targeted cancer therapies. Here we discuss the findings that implicate AMBRA1 as a core member of the cell cycle machinery.