DNA-binding protein Ikaros also known as Ikaros family zinc finger protein 1 is a protein that in humans is encoded by the IKZF1gene.[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]
↑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. PMID1439790.
↑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. PMC2680378. PMID19228925.
↑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. PMID9143685.
↑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.
↑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. PMID10766745.
↑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. PMID9560339.
↑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. PMID10204490.
↑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. PMID10218586.
↑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. PMID10978333.
↑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. PMID11959865.
Westman BJ, Mackay JP, Gell D (Oct 2002). "Ikaros: a key regulator of haematopoiesis". The International Journal of Biochemistry & Cell Biology. 34 (10): 1304–7. doi:10.1016/S1357-2725(02)00070-5. PMID12127581.
Molnár A, Wu P, Largespada DA, Vortkamp A, Scherer S, Copeland NG, Jenkins NA, Bruns G, Georgopoulos K (Jan 1996). "The Ikaros gene encodes a family of lymphocyte-restricted zinc finger DNA binding proteins, highly conserved in human and mouse". Journal of Immunology. 156 (2): 585–92. PMID8543809.
Nietfeld W, Meyerhans A (Jan 1996). "Cloning and sequencing of hIk-1, a cDNA encoding a human homologue of mouse Ikaros/LyF-1". Immunology Letters. 49 (1–2): 139–41. doi:10.1016/0165-2478(95)02479-4. PMID8964602.
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. PMID9560339.
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. PMID10204490.
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. PMID10218586.
Sun L, Goodman PA, Wood CM, Crotty ML, Sensel M, Sather H, Navara C, Nachman J, Steinherz PG, Gaynon PS, Seibel N, Vassilev A, Juran BD, Reaman GH, Uckun FM (Dec 1999). "Expression of aberrantly spliced oncogenic ikaros isoforms in childhood acute lymphoblastic leukemia". Journal of Clinical Oncology. 17 (12): 3753–66. PMID10577847.
Hosokawa Y, Maeda Y, Ichinohasama R, Miura I, Taniwaki M, Seto M (Apr 2000). "The Ikaros gene, a central regulator of lymphoid differentiation, fuses to the BCL6 gene as a result of t(3;7)(q27;p12) translocation in a patient with diffuse large B-cell lymphoma". Blood. 95 (8): 2719–21. PMID10753856.
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. PMID10766745.
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. PMID10978333.
Payne KJ, Nicolas JH, Zhu JY, Barsky LW, Crooks GM (Aug 2001). "Cutting edge: predominant expression of a novel Ikaros isoform in normal human hemopoiesis". Journal of Immunology. 167 (4): 1867–70. doi:10.4049/jimmunol.167.4.1867. PMID11489963.
Koipally J, Heller EJ, Seavitt JR, Georgopoulos K (Apr 2002). "Unconventional potentiation of gene expression by Ikaros". The Journal of Biological Chemistry. 277 (15): 13007–15. doi:10.1074/jbc.M111371200. PMID11799125.
Dorsam G, Goetzl EJ (Apr 2002). "Vasoactive intestinal peptide receptor-1 (VPAC-1) is a novel gene target of the hemolymphopoietic transcription factor Ikaros". The Journal of Biological Chemistry. 277 (16): 13488–93. doi:10.1074/jbc.M107922200. PMID11812772.