Stability of checkpoint kinase 2 is regulated via phosphorylation at serine 456.
Article Details
- CitationCopy to clipboard
Kass EM, Ahn J, Tanaka T, Freed-Pastor WA, Keezer S, Prives C
Stability of checkpoint kinase 2 is regulated via phosphorylation at serine 456.
J Biol Chem. 2007 Oct 12;282(41):30311-21. Epub 2007 Aug 21.
- PubMed ID
- 17715138 [ View in PubMed]
- Abstract
Checkpoint kinase 2 (Chk2), a DNA damage-activated protein kinase, is phosphorylated at Thr-68 by ataxia telangiectasia mutated leading to its activation by phosphorylation at several additional sites. Using mass spectrometry we identified a new Chk2 phosphorylation site at Ser-456. We show that phosphorylation of Ser-456 plays a role in the regulation of Chk2 stability particularly after DNA damage. Mutation of Ser-456 to alanine results in hyperubiquitination of Chk2 and dramatically reduced Chk2 stability. Furthermore, cells expressing S456A Chk2 show a reduction in the apoptotic response to DNA damage. These findings suggest a mechanism for stabilization of Chk2 in response to DNA damage via phosphorylation at Ser-456 and proteasome-dependent turnover of Chk2 protein via dephosphorylation of the same residue.