| Note | 1441 amino acids, highly acidic protein (pI 4.94), with calculated molecular mass of 164 kD. SDS-PAGE detected native RSF1 at molecular mass of 200 to 300 kD
Contain a DDT domain, Zinc finger PHD-type domain which was found in nuclear proteins thought to be involved in chromatin-mediated transcriptional regulation.
RSF1 also contains 3 nuclear localization signal near C-terminus. |
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| | Diagram of the RSF1 protein. |
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| Description | Using a variation of the yeast 2-hybrid screen aiming to identify proteins interacting with hepatitis B virus X protein (HBX), Shamay et al (2002a) cloned RSF1 from a spleen cDNA library. Therefore, the initial name of RSF1 was called Hepatitis B virus X-Associated Protein (HBXAP). Using 5'RACE, 3 splice variants were cloned and named HBXAP-alpha, -beta, -gamma, which contains 1431, 1400, and 1189 amino acids, respectively. By characterizing a protein remodeling complex RSF, Loyola A et al has identified two interacting subunits: RSF1 and SNF2H. They used peptide sequence information of RSF1 to clone the full-length cDNA. The deduced sequence contains 1441 amino acids which includes 252 additional amino acids at N-terminus as compared to HBXAP-gamma. Reconstitute experiment by isolating protein complex from coinfection of viruses caring each subunit can recapitulate the chromatin assembly ability and ATPase activity of native complex. They also showed that SNF2H binds to DNA independently of histones. However, RSF1 couldn't bind to DNA unless histones are present. |
| Expression | Highly expressed in heart, skeletal muscle, kidney, and placenta, and expressed weakly in brain and colon. |
| Localisation | Mainly located at cell nucleus. During mitosis, the expression in the nucleus is decreased. |
| Function | RSF1 functions as transcription coactivator when associated with hepatitis B virus X protein (HBX). Shamay et al (2002b) observed the direct interaction between the RSF1 variant, HBXAP-gamma, and HBX. HBXAP-gamma increased hepatitis B viral transcription in an HBX-dependent manner. Furthermore, in the presence of both HBX and HBXAP, the transcription of a nuclear factor kappa-B ( NFKB ) was significantly increased. However, in the presence of HBXAP alone, the transcription of a NFKB was decreased in a dose-dependent manner. Examination of HBXAP-gamma deletion mutants showed that the interaction between HBX and HBXAP-gamma was mediated by the PHD domain in HBXAP-gamma.
RSF1 functions as chromatin remodeling and spacing when associated with SNF2H. Loyola et al reconstituted the RSF complex by overexpressing two subunits, RSF1 and SNF2H. RSF1 assembled nucleosome randomly as a histone chaperone in the nuclei. The resulting nucleosomes were then redistributed into a regularly spaced nucleosome array by the ATP-utilizing nucleosome mobilization factor SNF2H. At the cellular level, Rsf1/SNF2H complex participated in chromatin remodeling by mobilizing nucleosomes in response to a variety of growth modifying signals and environmental cues. Sheu JJ et al found that the induction of RSF1 expression affected the molecular partnership of SNF2H and translocated SNF2H into nuclei where it colocalized with RSF1. To determine which domain in the RSF1 is involved in the binding to SNF2H, a series of RSF1-deletion mutants were generated. Only the fragment that contains DDT, Glu-rich, and PHD motifs could be immunoprecipitated with SNF2H. Ectopic expression of this RSF1 fragment disrupted RSF1/SNF2H complex and resulted in remarkable growth inhibition in ovarian cancer cells with RSF1 gene amplification and overexpression, but not in the cells without detectable RSF1 expression. This finding suggests that interaction between RSF1 and SNF2H may define a survival signal in the tumors overexpressing RSF1. |
| Hepatitis B virus pX interacts with HBXAP, a PHD finger protein to coactivate transcription. |
| Shamay M, Barak O, Doitsh G, Ben-Dor I, Shaul Y. |
| J Biol Chem. 2002b Mar 22;277(12):9982-8. Epub 2002 Jan 11. |
| PMID 11788598 |
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| HBXAP, a novel PHD-finger protein, possesses transcription repression activity. |
| Shamay M, Barak O, Shaul Y. |
| Genomics. 2002a Apr;79(4):523-9. |
| PMID 11944984 |
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| Functional analysis of the subunits of the chromatin assembly factor RSF. |
| Loyola A, Huang JY, LeRoy G, Hu S, Wang YH, Donnelly RJ, Lane WS, Lee SC, Reinberg D. |
| Mol Cell Biol. 2003 Oct;23(19):6759-68. |
| PMID 12972596 |
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| Amplification of a chromatin remodeling gene, Rsf-1/HBXAP, in ovarian carcinoma. |
| Shih IeM, Sheu JJ, Santillan A, Nakayama K, Yen MJ, Bristow RE, Vang R, Parmigiani G, Kurman RJ, Trope CG, Davidson B, Wang TL. |
| Proc Natl Acad Sci U S A. 2005 Sep 27;102(39):14004-9. Epub 2005 Sep 19. |
| PMID 16172393 |
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| Expression of Rsf-1, a chromatin-remodeling gene, in ovarian and breast carcinoma. |
| Mao TL, Hsu CY, Yen MJ, Gilks B, Sheu JJ, Gabrielson E, Vang R, Cope L, Kurman RJ, Wang TL, Shih IeM. |
| Hum Pathol. 2006 Sep;37(9):1169-75. Epub 2006 Jul 7. |
| PMID 16938522 |
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| The roles of human sucrose nonfermenting protein 2 homologue in the tumor-promoting functions of Rsf-1. |
| Sheu JJ, Choi JH, Yildiz I, Tsai FJ, Shaul Y, Wang TL, Shih IeM. |
| Cancer Res. 2008 Jun 1;68(11):4050-7. |
| PMID 18519663 |
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