FAK in the nucleus prevents VSMC proliferation by promoting p27 and p21 expression via Skp2 degradation.

ABSTRACT:

Aims

Vascular smooth muscle cells (VSMCs) normally exhibit a very low proliferative rate. Vessel injury triggers VSMC proliferation, in part, through focal adhesion kinase (FAK) activation, which increases transcription of cyclin D1, a key activator for cell cycle-dependent kinases (CDKs). At the same time, we also observe that FAK regulates the expression of the CDK inhibitors (CDKIs) p27 and p21. However, the mechanism of how FAK controls CDKIs in cell cycle progression is not fully understood.

Methods and results

We found that pharmacological and genetic FAK inhibition increased p27 and p21 by reducing stability of S-phase kinase-associated protein 2 (Skp2), which targets theCDKIs for degradation. FAK N-terminal domain interacts with Skp2 and an APC/C E3 ligase activator

SUBMITTER: Jeong K 

PROVIDER: S-EPMC8930076 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature