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Gene Review

TRERF1  -  transcriptional regulating factor 1

Homo sapiens

Synonyms: BCAR2, Breast cancer anti-estrogen resistance 2, HSA277276, RAPA, TREP132, ...
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Disease relevance of TRERF1


Psychiatry related information on TRERF1


High impact information on TRERF1

  • Here we show, by transforming self-incompatible plants of Brassica rapa with an SRK28 and an SLG28 transgene separately, that expression of SRK28 alone, but not SLG28 alone, conferred the ability to reject self (S28)-pollen on the transgenic plants [7].
  • In Brassica napus, accurately initiated pre-rRNA transcripts from one progenitor, Brassica rapa are detected readily, whereas transcripts from the approximately 3000 rRNA genes inherited from the other progenitor, Brassica oleracea, are undetectable [8].
  • The gene content of the recently duplicated B. rapa genome segments is identical, but intergenic sequences differ [9].
  • We show evidence for the dynamic and ongoing diploidization process by comparative analysis of the sequences of four paralogous Brassica rapa BAC clones and the homologous 124-kb segment of Arabidopsis thaliana chromosome 5 [9].
  • In a set of three S haplotypes, whose sequence identities of SP11 and SRK are fairly high, R. sativus S-6 showed the same recognition specificity as Brassica oleracea S-18 and a slightly different specificity from B. rapa S-52 [10].

Chemical compound and disease context of TRERF1

  • Taken together, these data identify TReP-132 as a coactivator of PR mediating the growth-inhibitory and differentiation effects of progesterone on breast cancer cells [11].
  • The toxicity profiles for CsA and RAPA are only partially overlapping, with RAPA toxicity consisting primarily of hyperlipidemia and myelodepression but without the nephrotoxicity, neurotoxicity, and hepatotoxicity, which are seen with CsA [12].

Biological context of TRERF1

  • Function of the transcriptional regulating protein of 132 kDa (TReP-132) on human P450scc gene expression [13].
  • Thus, these results together indicate the isolation of a novel zinc-finger transcriptional regulating protein of 132 kDa (TReP-132) involved in the regulation of P450scc gene expression [14].
  • We show here that TReP-132 plays a role in the control of cell proliferation [1].
  • In human HeLa cells, TReP-132 knockdown by using small interfering RNA resulted in increased G(1)-->S cell cycle progression [1].
  • Glutathione-S-transferase pull-down assays, bandshifts, and transient transfection assays showed that TReP-132 (another factor that can bind to -155/-131) does not interact with either LBP-1b or LBP-9, or influence their ability to induce or suppress transcription from the -155/-131 element [15].

Anatomical context of TRERF1

  • This transcriptional regulating protein of 132kDa (TReP-132) when expressed in HeLa cells was demonstrated to interact with the -155/-131 region in bandshift analysis, and tandem copies of this region was shown to confer activation of the heterologous HSV thymidine kinase minimal promoter [13].
  • Northern blot analysis demonstrate expression of two TReP-132 transcripts of 4.4 and 7.5 kilobase pairs in the thymus, adrenal cortex, and testis; and expression is also found in the steroidogenic JEG-3, NCI-H295, and MCF-7 cell lines [14].
  • As well, the progesterone-induced accumulation of lipid vacuoles was inhibited in the TReP-132-depleted cells [11].
  • Brassica rapa has three genes that encode proteins associated with different neutral lipids in plastids of specific tissues [16].
  • The immunosuppressive effect of Rapa in in vitro IgG, IgM, and IgA production by human lymphocytes was examined in this study [4].

Associations of TRERF1 with chemical compounds

  • Also, the "proximal activation domain" and the "AF-2 hexamer" motif of SF-1 are involved in interaction with TReP-132 [17].
  • In addition, TReP-132 knockdown resulted in enhanced cell proliferation and lowered p21 and p27 mRNA levels in the steroid-responsive and nonresponsive T-47D and MDA-MB-231 cell lines, respectively [1].
  • In addition, P450aro activity and mRNA levels are highly induced by TReP-132, whereas 3beta-hydroxysteroid dehydrogenase type II and P450c11aldo transcript levels are only slightly modulated [18].
  • The conversion of pregnenolone to downstream steroids following TReP-132 expression showed increased levels of glucocorticoids, C(19) steroids and estrogens [18].
  • Taken together, these results demonstrate that TReP-132 is a trans-acting factor of genes involved in adrenal glucocorticoid, C(19) steroid and estrogen production [18].

Regulatory relationships of TRERF1


Other interactions of TRERF1

  • Coexpression of CBP/p300 with TReP-132 further increased promoter activity, and the proteins were demonstrated to interact physically [13].
  • The transcriptional regulating protein of 132 kDa (TReP-132) has been identified in steroidogenic tissues, where it acts as a coactivator of steroidogenic factor 1 (SF-1) [1].
  • Finally, a statistic profiling of human breast tumor samples highlighted that expression of TReP-132 is correlated with p21 and p27 levels and is associated with lower tumor incidence and aggressiveness [1].

Analytical, diagnostic and therapeutic context of TRERF1

  • Immunocytochemistry analysis demonstrates localization of the HA-tagged TReP-132 protein in the nucleus [14].
  • Pull-down experiments demonstrated the interaction between TReP-132 and SF-1, and this was further confirmed in intact cells by coimmunoprecipitation/Western blot and two-hybrid analyses [17].
  • Molecular gene transfer techniques have been used to engineer the fatty acid composition of Brassica rapa and Brassica napus (canola) oil [19].
  • CONCLUSION: RAPA is a potent immunosuppressive agent for the treatment of refractory renal allograft rejection [20].
  • BACKGROUND: Sirolimus (Rapamune, rapamycin, RAPA) is a potent immunosuppressive drug that has reduced the rate of acute rejection episodes by more than 40% in phase III trials when added to an immunosuppression regimen of cyclosporine (CsA) and prednisone [3].


  1. TReP-132 controls cell proliferation by regulating the expression of the cyclin-dependent kinase inhibitors p21WAF1/Cip1 and p27Kip1. Gizard, F., Robillard, R., Barbier, O., Quatannens, B., Faucompré, A., Révillion, F., Peyrat, J.P., Staels, B., Hum, D.W. Mol. Cell. Biol. (2005) [Pubmed]
  2. The ABC's of comparative genomics in the Brassicaceae: building blocks of crucifer genomes. Schranz, M.E., Lysak, M.A., Mitchell-Olds, T. Trends Plant Sci. (2006) [Pubmed]
  3. Effect of sirolimus on the metabolism of apoB100- containing lipoproteins in renal transplant patients. Hoogeveen, R.C., Ballantyne, C.M., Pownall, H.J., Opekun, A.R., Hachey, D.L., Jaffe, J.S., Oppermann, S., Kahan, B.D., Morrisett, J.D. Transplantation (2001) [Pubmed]
  4. Inhibition of in vitro immunoglobulin production by rapamycin. Luo, H., Chen, H., Daloze, P., Chang, J.Y., St-Louis, G., Wu, J. Transplantation (1992) [Pubmed]
  5. Dyslipidemia during sirolimus therapy in liver transplant recipients occurs with concomitant cyclosporine but not tacrolimus. Trotter, J.F., Wachs, M.E., Trouillot, T.E., Bak, T., Kugelmas, M., Kam, I., Everson, G. Liver Transpl. (2001) [Pubmed]
  6. Increased allergen production in turnip (Brassica rapa) by treatments activating defense mechanisms. Hänninen, A.R., Mikkola, J.H., Kalkkinen, N., Turjanmaa, K., Ylitalo, L., Reunala, T., Palosuo, T. J. Allergy Clin. Immunol. (1999) [Pubmed]
  7. The S receptor kinase determines self-incompatibility in Brassica stigma. Takasaki, T., Hatakeyama, K., Suzuki, G., Watanabe, M., Isogai, A., Hinata, K. Nature (2000) [Pubmed]
  8. Epigenetic silencing of RNA polymerase I transcription: a role for DNA methylation and histone modification in nucleolar dominance. Chen, Z.J., Pikaard, C.S. Genes Dev. (1997) [Pubmed]
  9. Sequence-level analysis of the diploidization process in the triplicated FLOWERING LOCUS C region of Brassica rapa. Yang, T.J., Kim, J.S., Kwon, S.J., Lim, K.B., Choi, B.S., Kim, J.A., Jin, M., Park, J.Y., Lim, M.H., Kim, H.I., Lim, Y.P., Kang, J.J., Hong, J.H., Kim, C.B., Bhak, J., Bancroft, I., Park, B.S. Plant Cell (2006) [Pubmed]
  10. Diversification and alteration of recognition specificity of the pollen ligand SP11/SCR in self-incompatibility of Brassica and Raphanus. Sato, Y., Okamoto, S., Nishio, T. Plant Cell (2004) [Pubmed]
  11. TReP-132 Is a Novel Progesterone Receptor Coactivator Required for the Inhibition of Breast Cancer Cell Growth and Enhancement of Differentiation by Progesterone. Gizard, F., Robillard, R., Gross, B., Barbier, O., R??villion, F., Peyrat, J.P., Torpier, G., Hum, D.W., Staels, B. Mol. Cell. Biol. (2006) [Pubmed]
  12. Radioreceptor assay for sirolimus in patients with decreased platelet counts. Goodyear, N., Napoli, K.L., Murthy, J.N., Kahan, B.D., Soldin, S.J. Clin. Biochem. (1997) [Pubmed]
  13. Function of the transcriptional regulating protein of 132 kDa (TReP-132) on human P450scc gene expression. Gizard, F., El-Alfy, M., Duguay, Y., Lavallée, B., DeWitte, F., Staels, B., Beatty, B.G., Hum, D.W. Endocr. Res. (2002) [Pubmed]
  14. A novel zinc finger protein TReP-132 interacts with CBP/p300 to regulate human CYP11A1 gene expression. Gizard, F., Lavallée, B., DeWitte, F., Hum, D.W. J. Biol. Chem. (2001) [Pubmed]
  15. LBP proteins modulate SF1-independent expression of P450scc in human placental JEG-3 cells. Huang, N., Miller, W.L. Mol. Endocrinol. (2005) [Pubmed]
  16. Brassica rapa has three genes that encode proteins associated with different neutral lipids in plastids of specific tissues. Kim, H.U., Wu, S.S., Ratnayake, C., Huang, A.H. Plant Physiol. (2001) [Pubmed]
  17. The transcriptional regulating protein of 132 kDa (TReP-132) enhances P450scc gene transcription through interaction with steroidogenic factor-1 in human adrenal cells. Gizard, F., Lavallee, B., DeWitte, F., Teissier, E., Staels, B., Hum, D.W. J. Biol. Chem. (2002) [Pubmed]
  18. The transcriptional regulating protein of 132 kDa (TReP-132) differentially influences steroidogenic pathways in human adrenal NCI-H295 cells. Gizard, F., Teissier, E., Dufort, I., Luc, G., Luu-The, V., Staels, B., Hum, D.W. J. Mol. Endocrinol. (2004) [Pubmed]
  19. Modification of Brassica seed oil by antisense expression of a stearoyl-acyl carrier protein desaturase gene. Knutzon, D.S., Thompson, G.A., Radke, S.E., Johnson, W.B., Knauf, V.C., Kridl, J.C. Proc. Natl. Acad. Sci. U.S.A. (1992) [Pubmed]
  20. Sirolimus rescue therapy for refractory rejection in renal transplantation. Hong , J.C., Kahan, B.D. Transplantation (2001) [Pubmed]
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