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IKZF1

Introduction

“Ikaros transcription factor” redirects here. For other uses, see Icarus (disambiguation).

DNA-binding protein Ikaros also known as Ikaros family zinc finger protein 1 is a protein that in humans is encoded by the IKZF1 gene.[1][2][3] Ikaros displays crucial functions in the hematopoietic system and its loss of function has been linked to the development of lymphoid leukemia.[4] In particular, Ikaros has been found in recent years to be a major tumor suppressor involved in human B-cell acute lymphoblastic leukemia.[4] IKZF1 is upregulated in granulocytes, B cells, CD4 and CD8 T cells, and NK cells, and downregulated in erythroblasts, megakaryocytes and monocytes.[5] In Ikaros knockout mice, T cells but not B cells are generated late in mouse development due to late compensatory expression of the related gene Aiolos (IKZF3).[6] Ikaros point mutant mice are embryonic lethal due to anemia; they have severe defects in terminal erythrocyte and granulocyte differentiation, and excessive macrophage formation.[7] SNPs located near the 3′ region of IKZF1 in humans have been linked to susceptibility to childhood acute lymphoblastic leukemia (ALL) [8] as well as type 1 diabetes.[9] The two effects appear to be in opposite directions, with the allele marking susceptibility to ALL protecting from T1D and vice versa.[9]

Interactions

Interactions

IKZF1 has been shown to interact with:

References

References

  1. ↑ Georgopoulos K, Moore DD, Derfler B (Oct 1992). “Ikaros, an early lymphoid-specific transcription factor and a putative mediator for T cell commitment”. Science. 258 (5083): 808–12. doi:10.1126/science.1439790. PMID 1439790.
  2. ↑ Hahm K, Ernst P, Lo K, Kim GS, Turck C, Smale ST (Nov 1994). “The lymphoid transcription factor LyF-1 is encoded by specific, alternatively spliced mRNAs derived from the Ikaros gene”. Molecular and Cellular Biology. 14 (11): 7111–23. doi:10.1128/mcb.14.11.7111. PMC 359245. PMID 7935426.
  3. ↑ “Entrez Gene: IKZF1 IKAROS family zinc finger 1 (Ikaros)”.
  4. ↑ 4.0 4.1 Kastner P, Chan S (Jun 2011). “Role of Ikaros in T-cell acute lymphoblastic leukemia”. World Journal of Biological Chemistry. 2 (6): 108–14. doi:10.4331/wjbc.v2.i6.108. PMC 3135856. PMID 21765975.
  5. ↑ Watkins NA, Gusnanto A, de Bono B, De S, Miranda-Saavedra D, Hardie DL, Angenent WG, Attwood AP, Ellis PD, Erber W, Foad NS, Garner SF, Isacke CM, Jolley J, Koch K, Macaulay IC, Morley SL, Rendon A, Rice KM, Taylor N, Thijssen-Timmer DC, Tijssen MR, van der Schoot CE, Wernisch L, Winzer T, Dudbridge F, Buckley CD, Langford CF, Teichmann S, Göttgens B, Ouwehand WH (May 2009). “A HaemAtlas: characterizing gene expression in differentiated human blood cells”. Blood. 113 (19): e1–9. doi:10.1182/blood-2008-06-162958. PMC 2680378. PMID 19228925.
  6. ↑ Georgopoulos K, Winandy S, Avitahl N (1997). “The role of the Ikaros gene in lymphocyte development and homeostasis”. Annual Review of Immunology. 15: 155–76. doi:10.1146/annurev.immunol.15.1.155. PMID 9143685.
  7. ↑ Papathanasiou P, Perkins AC, Cobb BS, Ferrini R, Sridharan R, Hoyne GF, Nelms KA, Smale ST, Goodnow CC (July 2003). “Widespread failure of hematolymphoid differentiation caused by a recessive niche-filling allele of the Ikaros transcription factor”. Immunity. 19 (1): 131–44. doi:10.1016/s1074-7613(03)00168-7.
  8. ↑ Papaemmanuil E, Hosking FJ, Vijayakrishnan J, Price A, Olver B, Sheridan E, Kinsey SE, Lightfoot T, Roman E, Irving JA, Allan JM, Tomlinson IP, Taylor M, Greaves M, Houlston RS (Sep 2009). “Loci on 7p12.2, 10q21.2 and 14q11.2 are associated with risk of childhood acute lymphoblastic leukemia”. Nature Genetics. 41 (9): 1006–10. doi:10.1038/ng.430. PMC 4915548. PMID 19684604.
  9. ↑ 9.0 9.1 Swafford AD, Howson JM, Davison LJ, Wallace C, Smyth DJ, Schuilenburg H, Maisuria-Armer M, Mistry T, Lenardo MJ, Todd JA (Mar 2011). “An allele of IKZF1 (Ikaros) conferring susceptibility to childhood acute lymphoblastic leukemia protects against type 1 diabetes”. Diabetes. 60 (3): 1041–4. doi:10.2337/db10-0446. PMC 3046822. PMID 21270240.
  10. ↑ Koipally J, Georgopoulos K (Jun 2000). “Ikaros interactions with CtBP reveal a repression mechanism that is independent of histone deacetylase activity”. The Journal of Biological Chemistry. 275 (26): 19594–602. doi:10.1074/jbc.M000254200. PMID 10766745.
  11. ↑ 11.0 11.1 11.2 11.3 Koipally J, Renold A, Kim J, Georgopoulos K (Jun 1999). “Repression by Ikaros and Aiolos is mediated through histone deacetylase complexes”. The EMBO Journal. 18 (11): 3090–100. doi:10.1093/emboj/18.11.3090. PMC 1171390. PMID 10357820.
  12. ↑ 12.0 12.1 12.2 12.3 12.4 Koipally J, Georgopoulos K (Aug 2002). “A molecular dissection of the repression circuitry of Ikaros”. The Journal of Biological Chemistry. 277 (31): 27697–705. doi:10.1074/jbc.M201694200. PMID 12015313.
  13. ↑ Kelley CM, Ikeda T, Koipally J, Avitahl N, Wu L, Georgopoulos K, Morgan BA (Apr 1998). “Helios, a novel dimerization partner of Ikaros expressed in the earliest hematopoietic progenitors”. Current Biology. 8 (9): 508–15. doi:10.1016/s0960-9822(98)70202-7. PMID 9560339.
  14. ↑ Morgan B, Sun L, Avitahl N, Andrikopoulos K, Ikeda T, Gonzales E, Wu P, Neben S, Georgopoulos K (Apr 1997). “Aiolos, a lymphoid restricted transcription factor that interacts with Ikaros to regulate lymphocyte differentiation”. The EMBO Journal. 16 (8): 2004–13. doi:10.1093/emboj/16.8.2004. PMC 1169803. PMID 9155026.
  15. ↑ Kim J, Sif S, Jones B, Jackson A, Koipally J, Heller E, Winandy S, Viel A, Sawyer A, Ikeda T, Kingston R, Georgopoulos K (Mar 1999). “Ikaros DNA-binding proteins direct formation of chromatin remodeling complexes in lymphocytes”. Immunity. 10 (3): 345–55. doi:10.1016/s1074-7613(00)80034-5. PMID 10204490.
  16. ↑ Honma Y, Kiyosawa H, Mori T, Oguri A, Nikaido T, Kanazawa K, Tojo M, Takeda J, Tanno Y, Yokoya S, Kawabata I, Ikeda H, Wanaka A (Mar 1999). “Eos: a novel member of the Ikaros gene family expressed predominantly in the developing nervous system”. FEBS Letters. 447 (1): 76–80. doi:10.1016/s0014-5793(99)00265-3. PMID 10218586.
  17. ↑ Perdomo J, Holmes M, Chong B, Crossley M (Dec 2000). “Eos and pegasus, two members of the Ikaros family of proteins with distinct DNA binding activities”. The Journal of Biological Chemistry. 275 (49): 38347–54. doi:10.1074/jbc.M005457200. PMID 10978333.
  18. ↑ Koipally J, Georgopoulos K (Jun 2002). “Ikaros-CtIP interactions do not require C-terminal binding protein and participate in a deacetylase-independent mode of repression”. The Journal of Biological Chemistry. 277 (26): 23143–9. doi:10.1074/jbc.M202079200. PMID 11959865.
  19. ↑ Katsumura KR, Bresnick EH (April 2017). “The GATA factor revolution in hematology”. Blood. 129 (15): 2092–2102. doi:10.1182/blood-2016-09-687871. PMC 5391619. PMID 28179282.
Further reading

Further reading

External links