Format

Send to

Choose Destination
J Biol Chem. 2007 Oct 12;282(41):30311-21. Epub 2007 Aug 21.

Stability of checkpoint kinase 2 is regulated via phosphorylation at serine 456.

Author information

1
Department of Biological Sciences, Columbia University, New York, New York, 10027 and Cell Signaling Technology, Inc., Danvers, Massachusetts 01923.

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.

PMID:
17715138
DOI:
10.1074/jbc.M704642200
[Indexed for MEDLINE]
Free full text

Supplemental Content

Full text links

Icon for HighWire
Loading ...
Support Center