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

被引：40

作者：

Zhang, Dan ^{[1
,2
]}

Wang, Haibo ^{[2
]}

Sun, Mianen ^{[2
,3
]}

Yang, Jun ^{[2
]}

Zhang, Wei ^{[4
]}

Han, Suxia ^{[1
]}

Xu, Bo ^{[2
,5
,6
]}

机构：

[1] Xi An Jiao Tong Univ, Coll Med, Affiliated Hosp 1, Dept Oncol, Xian 710061, Shaanxi, Peoples R China

[2] Houston Methodist Res Inst, Dept Radiat Oncol, Houston, TX 77030 USA

[3] Univ Texas MD Anderson Canc Ctr, Dept Genitourinary Med Oncol, Houston, TX 77030 USA

[4] So Res Inst, Dept Organ Chem, Birmingham, AL 35205 USA

[5] So Res Inst, Dept Oncol, Birmingham, AL 35205 USA

[6] Univ Alabama Birmingham, Ctr Comprehens Canc, Birmingham, AL 35205 USA

来源：

CARCINOGENESIS | 2014年 / 35卷 / 08期

关键词：

BREAST-CANCER METASTASIS; UBIQUITIN LIGASE COMPLEX; DOUBLE-STRAND BREAKS; PROSTATE-CANCER; IONIZING IRRADIATION; GENOMIC INSTABILITY; S-PHASE; ATM; CHECKPOINT; SUPPRESSOR;

D O I：

10.1093/carcin/bgu022

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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 double-strand break sites and it forms nuclear foci after DNA damage. SPOP foci colocalize with gamma-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.

引用

页码：1691 / 1697

页数：7

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