Gfi1 (growth factor independence 1) is a transcriptionalrepressor that plays a critical role inhematopoiesis and in protecting hematopoietic cells against stress-inducedapoptosis. Gfi1 upregulates the expression of the nuclear proteinHemgn, which contributes to its anti-apoptotic activity. This upregulation is mediated through a specific 16-bp promoter region and is dependent on Gfi1’s interaction with the histone demethylaseLSD1.[7] Gfi1 repressesPU.1 transcription factor, and this repression precedes and correlates with the upregulation of Hemgn. The upregulation of Hemgn, in turn, contributes to the anti-apoptotic function of Gfi1, acting in ap53-independent manner.[7][8]
Gfi1 promotes cell survival by upregulating Hemgn through the repression of PU.1 thereby inhibiting apoptosis.[7] Gfi1 inhibits apoptosis induced by DNA damage, growth factor withdrawal, inhibitory cytokineTGF-β andMYC activation[8]
^"Human PubMed Reference:".National Center for Biotechnology Information, U.S. National Library of Medicine.
^"Mouse PubMed Reference:".National Center for Biotechnology Information, U.S. National Library of Medicine.
^Bell DW, Taguchi T, Jenkins NA, Gilbert DJ, Copeland NG, Gilks CB, et al. (July 1995). "Chromosomal localization of a gene, GF1, encoding a novel zinc finger protein reveals a new syntenic region between man and rodents".Cytogenetics and Cell Genetics.70 (3–4):263–267.doi:10.1159/000134048.PMID7789186.
^abBinod GC, Du P, Zhang Y, Yang L, Dong F (May 2025). "Bcl-xL is important for the antiapoptotic activity of Gfi1 and is upregulated by Gfi1 through hemgn".Journal of Immunology.214 (5). Baltimore, Md.:1046–1058.doi:10.1093/jimmun/vkae066.PMC 12123215.PMID40262274.
^McGhee L, Bryan J, Elliott L, Grimes HL, Kazanjian A, Davis JN, et al. (August 2003). "Gfi-1 attaches to the nuclear matrix, associates with ETO (MTG8) and histone deacetylase proteins, and represses transcription using a TSA-sensitive mechanism".Journal of Cellular Biochemistry.89 (5):1005–1018.doi:10.1002/jcb.10548.PMID12874834.S2CID25450754.
Osawa M, Yamaguchi T, Nakamura Y, Kaneko S, Onodera M, Sawada K, et al. (Oct 2002). "Erythroid expansion mediated by the Gfi-1B zinc finger protein: role in normal hematopoiesis".Blood.100 (8):2769–2777.doi:10.1182/blood-2002-01-0182.PMID12351384.
McGhee L, Bryan J, Elliott L, Grimes HL, Kazanjian A, Davis JN, et al. (Aug 2003). "Gfi-1 attaches to the nuclear matrix, associates with ETO (MTG8) and histone deacetylase proteins, and represses transcription using a TSA-sensitive mechanism".Journal of Cellular Biochemistry.89 (5):1005–1018.doi:10.1002/jcb.10548.PMID12874834.S2CID25450754.
Dwivedi PP, Anderson PH, Tilley WD, May BK, Morris HA (Mar 2007). "Role of oncoprotein growth factor independent-1 (GFI1) in repression of 25-hydroxyvitamin D 1alpha-hydroxylase (CYP27B1): a comparative analysis in human prostate cancer and kidney cells".The Journal of Steroid Biochemistry and Molecular Biology.103 (3–5):742–746.doi:10.1016/j.jsbmb.2006.12.014.PMID17207994.S2CID30600875.
Nakazawa Y, Suzuki M, Manabe N, Yamada T, Kihara-Negishi F, Sakurai T, et al. (May 2007). "Cooperative interaction between ETS1 and GFI1 transcription factors in the repression of Bax gene expression".Oncogene.26 (24):3541–3550.doi:10.1038/sj.onc.1210140.PMID17213822.S2CID30476328.
Marteijn JA, van der Meer LT, van Emst L, van Reijmersdal S, Wissink W, de Witte T, et al. (Nov 2007). "Gfi1 ubiquitination and proteasomal degradation is inhibited by the ubiquitin ligase Triad1".Blood.110 (9):3128–3135.doi:10.1182/blood-2006-11-058602.PMID17646546.S2CID19048016.
