Speckle-type POZ protein, SPOP, is involved in the DNA damage response.
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 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.
Department of Oncology, The First Affiliated Hospital of Xi'an Jiaotong University Medical College, Xi'An, Shaanxi 710061, China, Department of Radiation Oncology, Houston Methodist Research Institute, Houston, TX 77030, USA.
Dan
D
Zhang
Department of Radiation Oncology, Houston Methodist Research Institute, Houston, TX 77030, USA.
Haibo
H
Wang
Department of Radiation Oncology, Houston Methodist Research Institute, Houston, TX 77030, USA, Department of Genitourinary Medical Oncology, University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.
Mianen
M
Sun
Department of Radiation Oncology, Houston Methodist Research Institute, Houston, TX 77030, USA.
Jun
J
Yang
Department of Organic Chemistry and.
Wei
W
Zhang
Department of Oncology, The First Affiliated Hospital of Xi'an Jiaotong University Medical College, Xi'An, Shaanxi 710061, China.
Suxia
S
Han
Department of Radiation Oncology, Houston Methodist Research Institute, Houston, TX 77030, USA, Department of Oncology, Southern Research Institute, Birmingham, AL 35205, USA and Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, AL 35205, USA xu@sri.org.
Bo
B
Xu
D017209:Apoptosis / Q000502:physiology / Q000528:radiation effects; D064007:Ataxia Telangiectasia Mutated Proteins / Q000378:metabolism*; D015153:Blotting, Western; D049109:Cell Proliferation / Q000502:physiology / Q000528:radiation effects; D004249:DNA Damage / Q000235:genetics* / Q000528:radiation effects; D005455:Fluorescent Antibody Technique; D006801:Humans; D047468:Immunoprecipitation; D009369:Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D009687:Nuclear Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D011839:Radiation, Ionizing; D060888:Real-Time Polymerase Chain Reaction; D012097:Repressor Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured; D014410:Tumor Stem Cell Assay
D009687:Nuclear Proteins; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D012097:Repressor Proteins; C509761:SPOP protein, human; C576324:ATM protein, human; D064007:Ataxia Telangiectasia Mutated Proteins