Regulation of Bcl-xL-ATP Synthase Interaction by Mitochondrial Cyclin B1-Cyclin-Dependent Kinase-1 Determines Neuronal Survival.

ABSTRACT: The survival of postmitotic neurons needs continuous degradation of cyclin B1, a mitotic protein accumulated aberrantly in the damaged brain areas of Alzheimer's disease and stroked patients. Degradation of cyclin B1 takes place in the proteasome after ubiquitylation by the anaphase-promoting complex/cyclosome (APC/C)-cadherin 1 (Cdh1), an E3 ubiquitin ligase that is highly active in neurons. However, during excitotoxic damage-a hallmark of neurological disorders-APC/C-Cdh1 is inactivated, causing cyclin B1 stabilization and neuronal death through an unknown mechanism. Here, we show that an excitotoxic stimulus in rat cortical neurons in primary culture promotes cyclin B1 accumulation in the mitochondria, in which it binds to, and activates, cyclin-dependent kinase-1 (Cdk1). The cyclin B1-

SUBMITTER: Veas-Perez de Tudela M 

PROVIDER: S-EPMC6605197 | biostudies-literature | 2015 Jun

REPOSITORIES: biostudies-literature