Speckle-type POZ protein, SPOP, is involved in the DNA damage response

Dan Zhang, Haibo Wang, Mianen Sun, Jun Yang, Wei Zhang, Suxia Han, Bo Xu

Research output: Contribution to journalArticle

25 Scopus citations

Abstract

Speckle-type POZ protein (SPOP) is an adaptor of the cullin 3-based ubiquitin ligase responsible for the degradation of oncoproteins frequently overexpressed in many tumor cells. Altered expression and somatic mutations of SPOP have been observed in various tumor types with chromosomal aberrations, indicating a role of SPOP in maintaining genome stability, although a detailed mechanism remains unclear. Here, we show that SPOP is a component of the DNA damage response (DDR). SPOP is recruited to DNA doublestrand break sites and it forms nuclear foci after DNA damage. SPOP foci colocalize with γ-H2AX foci and are predominantly dependent on the activity of the ataxia-telangiectasia mutated (ATM) kinase. Furthermore, SPOP interacts with ATM in response to DNA damage. Finally, we demonstrate that knocking down of SPOP resulted in an impaired DDR and a hypersensitivity to ionizing irradiation. Together, we highlight a critical role of SPOP in the DDR.

Original languageEnglish (US)
Pages (from-to)1691-1697
Number of pages7
JournalCarcinogenesis
Volume35
Issue number8
DOIs
StatePublished - Aug 2014

ASJC Scopus subject areas

  • Cancer Research

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