Nuclear actin regulates cell proliferation and migration via inhibition of SRF and TEAD.

ABSTRACT: Actin dynamics regulate cell behaviour in response to physiological signals. Here we demonstrate a novel role for nuclear actin in inhibiting cell proliferation and migration. We demonstrate that physiological signals that elevate cAMP, which is anti-mitogenic in vascular smooth muscle cells, increases nuclear actin monomer levels. Expression of a nuclear-targeted polymerisation-defective actin mutant (NLS-Actin_R62D) inhibited proliferation and migration. Preventing nuclear actin monomer accumulation by enhancing its nuclear export or polymerisation reversed the anti-mitogenic and anti-migratory effects of cAMP. Transcriptomic analysis identified repression of proliferation and migration associated genes regulated by serum response factor (SRF) and TEA Domain (TEAD) transcriptio

SUBMITTER: McNeill MC 

PROVIDER: S-EPMC7262588 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature