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Spatio-Temporal Manipulation of Small GTPase Activity at Subcellular Level and on Timescale of Seconds in Living Cells
Published on: March 9, 2012
Rsf-1, a chromatin remodelling protein, interacts with cyclin E1 and promotes tumour development
Jim Jinn-Chyuan Sheu1, Jung Hye Choi, Bin Guan
1Department of Pathology, Gynecology and Obstetrics and Oncology, Johns Hopkins Medical Institutions, Baltimore, MD 21231, USA.
The Journal of Pathology
|February 5, 2013
Summary
Ruganization factor 1 (Rsf-1) and cyclin E1 collaborate to promote cancer cell proliferation and tumor formation. This interaction requires TP53 mutations, highlighting a key pathway in neoplastic transformation.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- The RSF1 gene, located at chromosome 11q13.5, is amplified in various human cancers, including ovarian carcinoma.
- Previous research indicated Rsf-1's necessity for cancer cell survival and tumor progression, but its role in tumor initiation remained unclear.
Purpose of the Study:
- To investigate the role of RSF1 in tumorigenesis.
- To identify proteins interacting with Rsf-1.
- To elucidate the collaborative mechanism between Rsf-1 and its interacting partners in cancer development.
Main Methods:
- Co-immunoprecipitation of Rsf-1 followed by nanoelectrospray mass spectrometry.
- Ectopic expression of Rsf-1 and cyclin E1 in TP53-mutated and wild-type cells.
- Domain mapping to identify the interacting region between Rsf-1 and cyclin E1.
Main Results:
- Cyclin E1 was identified as a major Rsf-1 interacting protein.
- Both RSF1 and CCNE1 are co-up-regulated in ovarian cancer tissues.
- Co-expression of Rsf-1 and cyclin E1 in TP53-mutated cells increased proliferation and tumor formation via CDK2 activation.
- Tumorigenesis was dependent on the presence of both Rsf-1 and cyclin E1, and a TP53 mutation.
Conclusions:
- Rsf-1 interacts with cyclin E1 to drive neoplastic transformation.
- TP53 mutations are essential for the tumor-promoting functions of the Rsf-1/cyclin E1 complex.
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