Molecular and genetic evidence for the role of AMBRA1 in suppressing S-phase entry and tumorigenesis.

ABSTRACT: AMBRA1, which was initially reported to be essential for nervous system development via autophagy and cell proliferation control, also functions as a tumor suppressor by regulating the ubiquitination of D-type cyclins through interaction with DDB1-Cullin4A/4 B E3 ligase. We had identified a missense mutation in AMBRA1 through exome analysis of a family with Cowden syndrome. The patient-type mutant showed reduced DDB1 binding and impaired cyclin D degradation. To investigate the physiological role of AMBRA1, we generated Ambra1 flox mice crossed with Rosa-Cre-ERT2-Tg mice. These inducible Ambra1 conditional knock out mice exhibited increased body weight, organ size, and enhanced S phase entry, with elevated cyclin D expression in a cell lineage- or differentiation-speci

SUBMITTER: Akatsuka H 

PROVIDER: S-EPMC12304916 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature