title: Rsf-1, a chromatin remodelling protein, interacts with cyclin E1 and promotes tumour development.
abstract: 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(mut)  RK3E 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.
authors: Department of Pathology, Gynecology and Obstetrics and Oncology, Johns Hopkins Medical Institutions, Baltimore, MD 21231, USA.
authors: Jim Jinn-Chyuan
authors: JJ
authors: Sheu
authors: Jung Hye
authors: JH
authors: Choi
authors: Bin
authors: B
authors: Guan
authors: Fuu-Jen
authors: FJ
authors: Tsai
authors: Chun-Hung
authors: CH
authors: Hua
authors: Ming-Tsung
authors: MT
authors: Lai
authors: Tian-Li
authors: TL
authors: Wang
authors: Ie-Ming
authors: IeM
authors: Shih
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002453:Cell Cycle; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic; D042002:Chromatin Assembly and Disassembly; D019927:Cyclin E / Q000235:genetics / Q000378:metabolism*; D051357:Cyclin-Dependent Kinase 2 / Q000235:genetics / Q000378:metabolism; D018284:Cystadenocarcinoma, Serous / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D004195:Disease Models, Animal; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D015513:Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D010051:Ovarian Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D025941:Protein Interaction Mapping; D017434:Protein Structure, Tertiary; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation
chemical_list: C475820:CCNE1 protein, human; D019927:Cyclin E; D009687:Nuclear Proteins; D015513:Oncogene Proteins; C452851:RSF1 protein, human; C495901:TP53 protein, human; D015534:Trans-Activators; D016159:Tumor Suppressor Protein p53; C495894:CDK2 protein, human; D051357:Cyclin-Dependent Kinase 2
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