Rsf-1, a chromatin remodelling protein, interacts with cyclin E1 and promotes tumour development

Jim Jinn Chyuan Sheu, Jung Hye Choi, Bin Guan, Fuu Jen Tsai, Chun Hung Hua, Ming Tsung Lai, Tian Li Wang, Ie Ming Shih

Research output: Contribution to journalArticlepeer-review

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 TP53mut 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 TP53wt 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.

Original languageEnglish (US)
Pages (from-to)559-568
Number of pages10
JournalJournal of Pathology
Volume229
Issue number4
DOIs
StatePublished - Mar 2013

Keywords

  • HBXAP
  • Rsf-1
  • TP53
  • cancer development
  • chromatin remodelling
  • cyclin E1

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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