Conserved Cdk inhibitors show unique structural responses to tyrosine phosphorylation.

ABSTRACT: Balanced proliferation-quiescence decisions are vital during normal development and in tissue homeostasis, and their dysregulation underlies tumorigenesis. Entry into proliferative cycles is driven by Cyclin/Cyclin-dependent kinases (Cdks). Conserved Cdk inhibitors (CKIs) p21^Cip1/Waf1, p27^Kip1, and p57^Kip2 bind to Cyclin/Cdks and inhibit Cdk activity. p27 tyrosine phosphorylation, in response to mitogenic signaling, promotes activation of CyclinD/Cdk4 and CyclinA/Cdk2. Tyrosine phosphorylation is conserved in p21 and p57, although the number of sites differs. We use molecular-dynamics simulations to compare the structural changes in Cyclin/Cdk/CKI trimers induced by single and multiple tyrosine phosphorylation in CKIs and their impact on CyclinD/Cdk4 and Cy

SUBMITTER: Swadling JB 

PROVIDER: S-EPMC9279356 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature