Abstract
Evaluation of: Tian B, Yang Q, Mao Z: Phosphorylation of ATM by Cdk5 mediates DNA damage signalling and regulates neuronal death. Nat. Cell Biol. 11(2), 211–218 (2009). This study demonstrates that Cdk5 phosphorylates ataxia-telangiectasia mutated protein (ATM) at Ser794 in postmitotic neurons when DNA damage is induced. Moreover, the authors describe that phosphorylation at Ser794 is required for autophosphorylation of ATM at Ser1981 and is necessary for its activation. They show that phosphorylation of ATM by Cdk5 plays a key role as a regulator of p53 and H2AX phosphorylation and function, which are direct targets of ATM. Cdk5–ATM pathway interruption protects neurons from cell death since it reduces cell cycle re-entry and the expression of PUMA and Bax, which are targets of p53.
Financial & competing interests disclosure
The authors are supported by grants from Spain‘s Ministerio de Educación y Ciencia (SAF2006–13092) and Fondo de Investigación Sanitaria, Instituto de Salud Carlos III (PI080400). We are grateful to the Generalitat de Catalunya for supporting research groups (2005/SGR00893) and to the Fundació la Marató TV3 (063230). Ester Verdaguer has a Beatriu de Pinós posdoctoral contract from Generalitat de Catalunya. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.
No writing assistance was utilized in the production of this manuscript