RRC ID 38413
著者 Wang HF, Takenaka K, Nakanishi A, Miki Y.
タイトル BRCA2 and nucleophosmin coregulate centrosome amplification and form a complex with the Rho effector kinase ROCK2.
ジャーナル Cancer Res
Abstract BRCA2 germline mutations account for the majority of heredity breast and ovarian cancer. Besides its role in DNA damage repair, BRCA2 also plays an important role in cytokinesis, transcription regulation, and cancer cell proliferation. Recently, we reported that BRCA2 localizes to centrosomes as well as nuclei and the dysfunction of BRCA2 in a centrosome causes abnormalities in cell division. Here, we identified a nucleolar phosphoprotein, nucleophosmin (NPM), as a novel BRCA2-associated protein. We also detected the binding of BRCA2 to ROCK2, an effector of Rho small GTPase. Because it is known that ROCK2 binds to NPM at centrosomes, these 3 proteins may form a complex. NPM-binding region was within amino acids 639-1,000 of BRCA2. Exogenous expression of this BRCA2 region resulted in aberrant centrosome amplification and a high frequency of multinucleated cells. Our results suggested that a complex consisting of BRCA2, NPM, and ROCK2 maintains the numerical integrity of centrosomes and accurate cell division and that dysfunction of this regulation might be involved in the tumorigenesis of breast cancer.
巻・号 71(1)
ページ 68-77
公開日 2011-1-1
DOI 10.1158/0008-5472.CAN-10-0030
PII 0008-5472.CAN-10-0030
PMID 21084279
MeSH Animals BRCA2 Protein / genetics BRCA2 Protein / metabolism BRCA2 Protein / physiology* Blotting, Western COS Cells Centrosome Chlorocebus aethiops Genes, BRCA2* Germ-Line Mutation HeLa Cells Humans Immunoprecipitation Microscopy, Fluorescence Nuclear Proteins / metabolism Nuclear Proteins / physiology* Nucleophosmin rho-Associated Kinases / metabolism*
IF 9.727
引用数 28
WOS 分野 ONCOLOGY
リソース情報
ヒト・動物細胞 COS-7(RCB0539) HeLa S3