The β-NAD⁺ salvage pathway and PKC-mediated signaling influence localized PARP-1 activity and CTCF Poly(ADP)ribosylation.

ABSTRACT: Poly(ADP)ribosylation (PARylation) of the chromatin architectural protein CTCF is critical for CTCF-dependent regulation of chromatin boundary and insulator elements. Loss of CTCF PARylation results in epigenetic silencing of certain tumor suppressor genes through destabilization of nearby chromatin boundaries. We investigated the metabolic and mechanistic processes that regulate PARP-1-mediated CTCF PARylation in human cancer cell lines and discovered a key role for the expression and activity of β-NAD+ salvage enzymes, NAMPT and NMNAT-1. These enzymes are downregulated in cells that exhibit reduced CTCF PARylation, resulting in a decreased concentration of nuclear β-NAD+. In these cells, decreased NMNAT-1 expression is enforced by a proteasome-mediated feedback loop resulting in degradat

SUBMITTER: Henderson DJP 

PROVIDER: S-EPMC5630287 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature