Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.

Phosphorylation of ATM by Cdk5 mediates DNA damage signalling and regulates neuronal death.

Tian B., Yang Q., Mao Z.

The phosphatidylinositol-3-kinase-like kinase ATM (ataxia-telangiectasia mutated) has a central role in coordinating DNA damage responses, including cell-cycle checkpoint control, DNA repair and apoptosis. Mutations of ATM cause a spectrum of defects ranging from neurodegeneration to cancer predisposition. However, the mechanism by which DNA damage activates ATM is poorly understood. Here we show that Cdk5 (cyclin-dependent kinase 5), activated by DNA damage, directly phosphorylates ATM at Ser 794 in post-mitotic neurons. Phosphorylation at Ser 794 precedes, and is required for, ATM autophosphorylation at Ser 1981, and activates ATM kinase activity. The Cdk5-ATM signal regulates phosphorylation and function of the ATM targets p53 and H2AX. Interruption of the Cdk5-ATM pathway attenuates DNA-damage-induced neuronal cell cycle re-entry and expression of the p53 targets PUMA and Bax, protecting neurons from death. Thus, activation of Cdk5 by DNA damage serves as a critical signal to initiate the ATM response and regulate ATM-dependent cellular processes.

Nat. Cell Biol. 11:211-218(2009) [PubMed] [Europe PMC]

UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

We'd like to inform you that we have updated our Privacy Notice to comply with Europe’s new General Data Protection Regulation (GDPR) that applies since 25 May 2018.

Do not show this banner again