Regulation of Chk2 ubiquitination and signaling through autophosphorylation of serine 379

Christine M. Lovly, Ling Yan, Christine E. Ryan, Saeko Takada, Helen Piwnica-Worms

Research output: Contribution to journalArticlepeer-review

30 Scopus citations


The Chk2 protein kinase protects genome integrity by promoting cell cycle arrest or apoptosis in response to DNA double-strand breaks, and Chk2 mutations are found in both familial and sporadic cancers. Exposure of cells to ionizing radiation (IR) or radiomimetic drugs induces Chk2 phosphorylation by ATM, followed by Chk2 oligomerization, auto-/transphosphorylation, and activation. Here we demonstrate that Chk2 is ubiquitinated upon activation and that this requires Chk2 kinase activity. Serine 379 (S379) was identified as a novel IR-inducible autophosphorylation site required for ubiquitination of Chk2 by a Cullin 1-containing E3 ligase complex. Importantly, S379 was required for Chk2 to induce apoptosis in cells with DNA double-strand breaks. Thus, auto-/transphosphorylation of S379 is required for Chk2 ubiquitination and effector function.

Original languageEnglish (US)
Pages (from-to)5874-5885
Number of pages12
JournalMolecular and cellular biology
Issue number19
StatePublished - Oct 2008


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