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Gene Review

Gfi1  -  growth factor independent 1

Mus musculus

Synonyms: AW495828, Gfi-1, Growth factor independent protein 1, Pal-1, Pal1, ...
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Disease relevance of Gfi1

  • Heightened expression of Gfi1 distinguishes MZL from other lymphoma types [1].
  • Inflammatory reactions and severe neutropenia in mice lacking the transcriptional repressor Gfi1 [2].
  • Gfi1-deficient mice responded to a pulmonary P. aeruginosa infection with uncontrolled pulmonary release of interleukin (IL)-1 and tumour necrosis factor (TNF)-alpha, sepsis and death, which were delayed by injection of IL-1- and TNF-alpha-neutralizing antibodies [3].
  • Regulation of pulmonary Pseudomonas aeruginosa infection by the transcriptional repressor Gfi1 [3].
  • Gfi1(-/-) mice show a very strong systemic response to the endotoxin LPS and die rapidly within 36 h with symptoms of septic shock [4].

Psychiatry related information on Gfi1


High impact information on Gfi1


Biological context of Gfi1

  • Mice lacking Gfi1 show reduced thymic cellularity due to an increased cell death rate, lack of proliferation, and a differentiation block in the very early uncommitted CD4-/CD8-/c-Kit+ cytokine-dependent T cell progenitors that have not yet initiated VDJ recombination [7].
  • In addition, Gfi1-deficient mice show increased major histocompatibility complex class I-restricted positive selection and develop significantly more CD8+ cells suggesting a requirement of Gfi1 for a correct CD4/CD8 lineage decision [7].
  • The zinc finger transcription factor Gfi1, implicated in lymphomagenesis, is required for inner ear hair cell differentiation and survival [8].
  • Furthermore, Gfi1 mutant mice lose all cochlear hair cells just prior to and soon after birth through apoptosis [8].
  • We show that Gfi1 mRNA is expressed in many areas that give rise to neuronal cells during embryonic development in mouse, and that Gfi1 protein has a more restricted expression pattern [8].

Anatomical context of Gfi1


Associations of Gfi1 with chemical compounds


Physical interactions of Gfi1

  • The repression is direct and depends on several Gfi-1-binding sites in the p53-inducible Bax promoter [13].

Regulatory relationships of Gfi1


Other interactions of Gfi1

  • To validate this result, we performed semi-quantitative RT-PCR and in situ hybridizations for Gfi1 on wild-type and Pou4f3 mutant mice [9].
  • However, neither Gfi1 nor Gfi1b has been implicated in nervous system development, even though their invertebrate homologues, senseless in Drosophila and pag-3 in C. elegans are expressed and required in the nervous system [8].
  • Evi5 thus encodes a gene separate from Gfi1 that may also be involved in T-cell disease [14].
  • Proviral activation of the Pim and Myc genes but not the Gfi1 gene were frequently observed in these tumors [15].
  • Gfi1 was first identified as causing interleukin 2-independent growth in T cells and lymphomagenesis in mice [8].

Analytical, diagnostic and therapeutic context of Gfi1


  1. High-throughput retroviral tagging for identification of genes involved in initiation and progression of mouse splenic marginal zone lymphomas. Shin, M.S., Fredrickson, T.N., Hartley, J.W., Suzuki, T., Akagi, K., Agaki, K., Morse, H.C. Cancer Res. (2004) [Pubmed]
  2. Inflammatory reactions and severe neutropenia in mice lacking the transcriptional repressor Gfi1. Karsunky, H., Zeng, H., Schmidt, T., Zevnik, B., Kluge, R., Schmid, K.W., Dührsen, U., Möröy, T. Nat. Genet. (2002) [Pubmed]
  3. Regulation of pulmonary Pseudomonas aeruginosa infection by the transcriptional repressor Gfi1. Grassmé, H., Jin, J., Wilker, B., von Kürthy, G., Wick, W., Weller, M., Möröy, T., Gulbins, E. Cell. Microbiol. (2006) [Pubmed]
  4. The zinc finger protein Gfi1 acts upstream of TNF to attenuate endotoxin-mediated inflammatory responses in the lung. Jin, J., Zeng, H., Schmid, K.W., Toetsch, M., Uhlig, S., Möröy, T. Eur. J. Immunol. (2006) [Pubmed]
  5. Zinc finger protein GFI-1 has low oncogenic potential but cooperates strongly with pim and myc genes in T-cell lymphomagenesis. Schmidt, T., Karsunky, H., Gau, E., Zevnik, B., Elsässer, H.P., Möröy, T. Oncogene (1998) [Pubmed]
  6. The AXH domain of Ataxin-1 mediates neurodegeneration through its interaction with Gfi-1/Senseless proteins. Tsuda, H., Jafar-Nejad, H., Patel, A.J., Sun, Y., Chen, H.K., Rose, M.F., Venken, K.J., Botas, J., Orr, H.T., Bellen, H.J., Zoghbi, H.Y. Cell (2005) [Pubmed]
  7. The transcriptional repressor Gfi1 affects development of early, uncommitted c-Kit+ T cell progenitors and CD4/CD8 lineage decision in the thymus. Yücel, R., Karsunky, H., Klein-Hitpass, L., Möröy, T. J. Exp. Med. (2003) [Pubmed]
  8. The zinc finger transcription factor Gfi1, implicated in lymphomagenesis, is required for inner ear hair cell differentiation and survival. Wallis, D., Hamblen, M., Zhou, Y., Venken, K.J., Schumacher, A., Grimes, H.L., Zoghbi, H.Y., Orkin, S.H., Bellen, H.J. Development (2003) [Pubmed]
  9. Transcription profiling of inner ears from Pou4f3(ddl/ddl) identifies Gfi1 as a target of the Pou4f3 deafness gene. Hertzano, R., Montcouquiol, M., Rashi-Elkeles, S., Elkon, R., Yücel, R., Frankel, W.N., Rechavi, G., Möröy, T., Friedman, T.B., Kelley, M.W., Avraham, K.B. Hum. Mol. Genet. (2004) [Pubmed]
  10. Evidence implicating Gfi-1 and Pim-1 in pre-T-cell differentiation steps associated with beta-selection. Schmidt, T., Karsunky, H., Rödel, B., Zevnik, B., Elsässer, H.P., Möröy, T. EMBO J. (1998) [Pubmed]
  11. Gfi-1 encodes a nuclear zinc finger protein that binds DNA and functions as a transcriptional repressor. Zweidler-Mckay, P.A., Grimes, H.L., Flubacher, M.M., Tsichlis, P.N. Mol. Cell. Biol. (1996) [Pubmed]
  12. Gfi-1 restricts proliferation and preserves functional integrity of haematopoietic stem cells. Hock, H., Hamblen, M.J., Rooke, H.M., Schindler, J.W., Saleque, S., Fujiwara, Y., Orkin, S.H. Nature (2004) [Pubmed]
  13. The Gfi-1 protooncoprotein represses Bax expression and inhibits T-cell death. Grimes, H.L., Gilks, C.B., Chan, T.O., Porter, S., Tsichlis, P.N. Proc. Natl. Acad. Sci. U.S.A. (1996) [Pubmed]
  14. Proviral integrations at the Evi5 locus disrupt a novel 90 kDa protein with homology to the Tre2 oncogene and cell-cycle regulatory proteins. Liao, X., Du, Y., Morse, H.C., Jenkins, N.A., Copeland, N.G. Oncogene (1997) [Pubmed]
  15. Pertubation of B and T cell development and predisposition to lymphomagenesis in Emu Bmi1 transgenic mice require the Bmi1 RING finger. Alkema, M.J., Jacobs, H., van Lohuizen, M., Berns, A. Oncogene (1997) [Pubmed]
  16. Transcription factor Gfi1 regulates self-renewal and engraftment of hematopoietic stem cells. Zeng, H., Yücel, R., Kosan, C., Klein-Hitpass, L., Möröy, T. EMBO J. (2004) [Pubmed]
  17. Diminished proteasomal degradation results in accumulation of Gfi1 protein in monocytes. Marteijn, J.A., van der Meer, L.T., Van Emst, L., de Witte, T., Jansen, J.H., van der Reijden, B.A. Blood (2007) [Pubmed]
  18. A house fly gene homologous to the zinc finger proto-oncogene Gfi-1. Kasai, S., Scott, J.G. Biochem. Biophys. Res. Commun. (2001) [Pubmed]
  19. Gfi-1 oncoproteins in hematopoiesis. Duan, Z., Horwitz, M. Hematology (2003) [Pubmed]
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