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Rsf‐1, a chromatin remodelling protein, interacts with cyclin E1 and promotes tumour development
Author(s) -
Sheu Jim JinnChyuan,
Choi Jung Hye,
Guan Bin,
Tsai FuuJen,
Hua ChunHung,
Lai MingTsung,
Wang TianLi,
Shih IeMing
Publication year - 2013
Publication title -
the journal of pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.964
H-Index - 184
eISSN - 1096-9896
pISSN - 0022-3417
DOI - 10.1002/path.4147
Subject(s) - cyclin e1 , cyclin d , cyclin , ectopic expression , biology , cancer research , cyclin a , cyclin e , cyclin b , cyclin dependent kinase , chromatin , cyclin b1 , cell cycle , cyclin a2 , microbiology and biotechnology , cyclin d1 , cancer , gene , cyclin dependent kinase 1 , genetics
Chromosome 11q13.5 containing RSF1 ( HBXAP ), a gene involved in chromatin remodelling, is amplified in several human cancers including ovarian carcinoma. Our previous studies demonstrated requirement of Rsf‐1 for cell survival in cancer cells, which contributed to tumour progression; however, its role in tumourigenesis has not yet been elucidated. In this study, we co‐immunoprecipitated proteins with Rsf‐1 followed by nanoelectrospray mass spectrometry and identified cyclin E1 , besides SNF2H , as one of the major Rsf‐1 interacting proteins. Like RSF1 , CCNE1 is frequently amplified in ovarian cancer, and both Rsf‐1 and cyclin E1 were found co‐up‐regulated in ovarian cancer tissues. Ectopic expression of Rsf‐1 and cyclin E1 in non‐tumourigenic TP53 mutRK3E cells led to an increase in cellular proliferation and tumour formation by activating cyclin E1 ‐associated kinase ( CDK2 ). Tumourigenesis was not detected if either cyclin E1 or Rsf‐1 was expressed, or they were expressed in a TP53 wt background. Domain mapping showed that cyclin E1 interacted with the first 441 amino acids of Rsf‐1. Ectopic expression of this truncated domain significantly suppressed G1 /S‐phase transition, cellular proliferation, and tumour formation of RK3E‐p53 R175H /Rsf‐1/cyclin E1 cells. The above findings suggest that Rsf‐1 interacts and collaborates with cyclin E1 in neoplastic transformation and TP53 mutations are a prerequisite for tumour‐promoting functions of the RSF /cyclin E1 complex.