RBR-type E3 ubiquitin ligase RNF144A targets PARP1 for ubiquitin-dependent degradation and regulates PARP inhibitor sensitivity in breast cancer cells.

ABSTRACT: Poly(ADP-ribose) polymerase 1 (PARP1), a critical DNA repair protein, is frequently upregulated in breast tumors with a key role in breast cancer progression. Consequently, PARP inhibitors have emerged as promising therapeutics for breast cancers with DNA repair deficiencies. However, relatively little is known about the regulatory mechanism of PARP1 expression and the determinants of PARP inhibitor sensitivity in breast cancer cells. Here, we report that ring finger protein 144A (RNF144A), a RING-between-RING (RBR)-type E3 ubiquitin ligase with an unexplored functional role in human cancers, interacts with PARP1 through its carboxy-terminal region containing the transmembrane domain, and targets PARP1 for ubiquitination and subsequent proteasomal degradation. Moreover, induced expression

SUBMITTER: Zhang Y 

PROVIDER: S-EPMC5706891 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature