IKZF1

IKAROS family zinc finger 1 (Ikaros)
Identifiers
Symbols	IKZF1; Hs.54452; IK1; IKAROS; LYF1; PRO0758; ZNFN1A1; hIk-1
External IDs	OMIM: 603023 MGI: 1342540 HomoloGene: 55948 GeneCards: IKZF1 Gene
Gene Ontology
Molecular function	• DNA binding; • sequence-specific DNA binding transcription factor activity; • zinc ion binding; • sequence-specific DNA binding; • metal ion binding; • protein heterodimerization activity;
Cellular component	• intracellular; • nucleus; • centromeric heterochromatin; • cytoplasm;
Biological process	• natural killer cell differentiation; • cell cycle; • multicellular organismal development; • mesoderm development; • chromatin modification; • hemopoiesis; • B cell differentiation; • T cell differentiation; • forebrain development; • positive regulation of multicellular organism growth; • positive regulation of neutrophil differentiation; • positive regulation of transcription from RNA polymerase II promoter; • lymph node development; • thymus development; • Peyer's patch development; • gland development; • positive regulation of NK T cell differentiation; • retina development in camera-type eye;
	Sources: Amigo / QuickGO
RNA expression pattern
	More reference expression data
Orthologs

From Wikipedia, the free encyclopedia

Jump to: navigation, search

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] SNPs located near the 3' region of IKZF1 in humans have been linked to susceptibility to childhood acute lymphoblastic leukemia (ALL) ^[7] as well as type 1 diabetes.^[8] Interesting, the two effects appear to be in opposite directions, with the allele marking susceptibility to ALL protecting from T1D and vice versa.^[8]

[edit] Interactions

IKZF1 has been shown to interact with IKZF2 ^[9], IKZF3^[10]^[11]^[12], IKZF4^[13]^[14], Histone deacetylase 5,^[15] HDAC1,^[11]^[15] HDAC7A,^[15] SIN3B,^[11]^[15] SIN3A,^[16]^[11]^[15] and CTBP1.^[17]

[edit] References

^ Georgopoulos K, Moore DD, Derfler B (Dec 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.
^ 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". Mol Cell Biol 14 (11): 7111–23. PMC 359245. PMID 7935426. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=359245.
^ "Entrez Gene: IKZF1 IKAROS family zinc finger 1 (Ikaros)". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=10320.
^ ^a ^b Kastner P, Chan S (Jun 2011). "Role of Ikaros in T-cell acute lymphoblastic leukemia". World J Biol Chem 2 (6): 108–14. doi:10.4331/wjbc.v2.i6.108. PMC 3135856. PMID 21765975. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3135856.
^ 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; Bloodomics Consortium. (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. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2680378.
^ Georgopoulos K, Winandy S, Avitahl N. (1997). "The role of the Ikaros gene in lymphocyte development and homeostasis.". Ann Rev Immunol. 15: 155–76. doi:10.1146/annurev.immunol.15.1.155. PMID 9143685.
^ 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.". Ann Rev Immunol. 41 (9): 1006–10. doi:10.1038/ng.430. PMID 19684604.
^ ^a ^b Swafford AD, Howson JM, Davison LJ, Wallace C, Smyth DJ, Schuilenburg H, Maisuria-Armer M, Mistry T, Lenardo MJ, Todd JA. (Feb 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. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3046822.
^ 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". Curr Biol 8 (9): 508–915. doi:10.1016/S0960-9822(98)70202-7. PMID 9560339.
^ 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.". EMBO 16 (8): 2004–13. doi:10.1093/emboj/16.8.2004. PMC 1169803. PMID 9155026. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1169803.
^ ^a ^b ^c ^d Koipally J, Renold A, Kim J, Georgopoulos K. (Jun 1999). "Repression by Ikaros and Aiolos is mediated through histone deacetylase complexes.". EMBO 18 (11): 3090–100. doi:10.1093/emboj/18.11.3090. PMC 1171390. PMID 10357820. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1171390.
^ 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.
^ 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 Lett. (NETHERLANDS) 447 (1): 76–80. doi:10.1016/S0014-5793(99)00265-3. ISSN 0014-5793. PMID 10218586.
^ 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". J. Biol. Chem. (UNITED STATES) 275 (49): 38347–54. doi:10.1074/jbc.M005457200. ISSN 0021-9258. PMID 10978333.
^ ^a ^b ^c ^d ^e Koipally, Joseph; Georgopoulos Katia (Aug. 2002). "A molecular dissection of the repression circuitry of Ikaros". J. Biol. Chem. (United States) 277 (31): 27697–705. doi:10.1074/jbc.M201694200. ISSN 0021-9258. PMID 12015313.
^ Koipally, Joseph; Georgopoulos Katia (Jun. 2002). "Ikaros-CtIP interactions do not require C-terminal binding protein and participate in a deacetylase-independent mode of repression". J. Biol. Chem. (United States) 277 (26): 23143–9. doi:10.1074/jbc.M202079200. ISSN 0021-9258. PMID 11959865.
^ Koipally, J; Georgopoulos K (Jun. 2000). "Ikaros interactions with CtBP reveal a repression mechanism that is independent of histone deacetylase activity". J. Biol. Chem. (UNITED STATES) 275 (26): 19594–602. doi:10.1074/jbc.M000254200. ISSN 0021-9258. PMID 10766745.

[edit] Further reading

Tonnelle C, Calmels B, Maroc C et al. (2003). "Ikaros gene expression and leukemia". Leuk. Lymphoma 43 (1): 29–35. doi:10.1080/10428190210186. PMID 11908734.
Westman BJ, Mackay JP, Gell D (2002). "Ikaros: a key regulator of haematopoiesis". Int. J. Biochem. Cell Biol. 34 (10): 1304–7. doi:10.1016/S1357-2725(02)00070-5. PMID 12127581.
Molnár A, Wu P, Largespada DA et al. (1996). "The Ikaros gene encodes a family of lymphocyte-restricted zinc finger DNA binding proteins, highly conserved in human and mouse". J. Immunol. 156 (2): 585–92. PMID 8543809.
Nietfeld W, Meyerhans A (1996). "Cloning and sequencing of hIk-1, a cDNA encoding a human homologue of mouse Ikaros/LyF-1". Immunol. Lett. 49 (1–2): 139–41. doi:10.1016/0165-2478(95)02479-4. PMID 8964602.
Morgan B, Sun L, Avitahl N et al. (1997). "Aiolos, a lymphoid restricted transcription factor that interacts with Ikaros to regulate lymphocyte differentiation". EMBO J. 16 (8): 2004–13. doi:10.1093/emboj/16.8.2004. PMC 1169803. PMID 9155026. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1169803.
Kelley CM, Ikeda T, Koipally J et al. (1998). "Helios, a novel dimerization partner of Ikaros expressed in the earliest hematopoietic progenitors". Curr. Biol. 8 (9): 508–15. doi:10.1016/S0960-9822(98)70202-7. PMID 9560339.
Sun L, Heerema N, Crotty L et al. (1999). "Expression of dominant-negative and mutant isoforms of the antileukemic transcription factor Ikaros in infant acute lymphoblastic leukemia". Proc. Natl. Acad. Sci. U.S.A. 96 (2): 680–5. doi:10.1073/pnas.96.2.680. PMC 15196. PMID 9892693. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=15196.
Kim J, Sif S, Jones B et al. (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.
Honma Y, Kiyosawa H, Mori T et al. (1999). "Eos: a novel member of the Ikaros gene family expressed predominantly in the developing nervous system". FEBS Lett. 447 (1): 76–80. doi:10.1016/S0014-5793(99)00265-3. PMID 10218586.
Koipally J, Renold A, Kim J, Georgopoulos K (1999). "Repression by Ikaros and Aiolos is mediated through histone deacetylase complexes". EMBO J. 18 (11): 3090–100. doi:10.1093/emboj/18.11.3090. PMC 1171390. PMID 10357820. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1171390.
Sun L, Goodman PA, Wood CM et al. (2000). "Expression of aberrantly spliced oncogenic ikaros isoforms in childhood acute lymphoblastic leukemia". J. Clin. Oncol. 17 (12): 3753–66. PMID 10577847.
Hosokawa Y, Maeda Y, Ichinohasama R et al. (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. PMID 10753856.
Koipally J, Georgopoulos K (2000). "Ikaros interactions with CtBP reveal a repression mechanism that is independent of histone deacetylase activity". J. Biol. Chem. 275 (26): 19594–602. doi:10.1074/jbc.M000254200. PMID 10766745.
Perdomo J, Holmes M, Chong B, Crossley M (2001). "Eos and pegasus, two members of the Ikaros family of proteins with distinct DNA binding activities". J. Biol. Chem. 275 (49): 38347–54. doi:10.1074/jbc.M005457200. PMID 10978333.
Payne KJ, Nicolas JH, Zhu JY et al. (2001). "Cutting edge: predominant expression of a novel Ikaros isoform in normal human hemopoiesis". J. Immunol. 167 (4): 1867–70. PMID 11489963.
Koipally J, Heller EJ, Seavitt JR, Georgopoulos K (2002). "Unconventional potentiation of gene expression by Ikaros". J. Biol. Chem. 277 (15): 13007–15. doi:10.1074/jbc.M111371200. PMID 11799125.
Dorsam G, Goetzl EJ (2002). "Vasoactive intestinal peptide receptor-1 (VPAC-1) is a novel gene target of the hemolymphopoietic transcription factor Ikaros". J. Biol. Chem. 277 (16): 13488–93. doi:10.1074/jbc.M107922200. PMID 11812772.

[edit] External links

MeSH IKZF1+protein,+human

This article on a gene on chromosome 7 is a stub. You can help Wikipedia by expanding it.

[pmid1439790-0] Georgopoulos K, Moore DD, Derfler B (Dec 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.

[pmid7935426-1] 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". Mol Cell Biol 14 (11): 7111–23. PMC 359245. PMID 7935426. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=359245.

[entrez-2] "Entrez Gene: IKZF1 IKAROS family zinc finger 1 (Ikaros)". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=10320.

[pmid21765975-3] Kastner P, Chan S (Jun 2011). "Role of Ikaros in T-cell acute lymphoblastic leukemia". World J Biol Chem 2 (6): 108–14. doi:10.4331/wjbc.v2.i6.108. PMC 3135856. PMID 21765975. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3135856.

[pmid19228925-4] 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; Bloodomics Consortium. (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. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2680378.

[pmid9143685-5] Georgopoulos K, Winandy S, Avitahl N. (1997). "The role of the Ikaros gene in lymphocyte development and homeostasis.". Ann Rev Immunol. 15: 155–76. doi:10.1146/annurev.immunol.15.1.155. PMID 9143685.

[pmid19684604-6] 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.". Ann Rev Immunol. 41 (9): 1006–10. doi:10.1038/ng.430. PMID 19684604.

[pmid21270240-7] Swafford AD, Howson JM, Davison LJ, Wallace C, Smyth DJ, Schuilenburg H, Maisuria-Armer M, Mistry T, Lenardo MJ, Todd JA. (Feb 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. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3046822.

[pmid9560339-8] 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". Curr Biol 8 (9): 508–915. doi:10.1016/S0960-9822(98)70202-7. PMID 9560339.

[9] 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.". EMBO 16 (8): 2004–13. doi:10.1093/emboj/16.8.2004. PMC 1169803. PMID 9155026. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1169803.

[pmid10357820-10] Koipally J, Renold A, Kim J, Georgopoulos K. (Jun 1999). "Repression by Ikaros and Aiolos is mediated through histone deacetylase complexes.". EMBO 18 (11): 3090–100. doi:10.1093/emboj/18.11.3090. PMC 1171390. PMID 10357820. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1171390.

[pmid10204490-11] 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.

[pmid10218586-12] 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 Lett. (NETHERLANDS) 447 (1): 76–80. doi:10.1016/S0014-5793(99)00265-3. ISSN 0014-5793. PMID 10218586.

[pmid10978333-13] 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". J. Biol. Chem. (UNITED STATES) 275 (49): 38347–54. doi:10.1074/jbc.M005457200. ISSN 0021-9258. PMID 10978333.

[pmid12015313-14] Koipally, Joseph; Georgopoulos Katia (Aug. 2002). "A molecular dissection of the repression circuitry of Ikaros". J. Biol. Chem. (United States) 277 (31): 27697–705. doi:10.1074/jbc.M201694200. ISSN 0021-9258. PMID 12015313.

[pmid11959865-15] Koipally, Joseph; Georgopoulos Katia (Jun. 2002). "Ikaros-CtIP interactions do not require C-terminal binding protein and participate in a deacetylase-independent mode of repression". J. Biol. Chem. (United States) 277 (26): 23143–9. doi:10.1074/jbc.M202079200. ISSN 0021-9258. PMID 11959865.

[pmid10766745-16] Koipally, J; Georgopoulos K (Jun. 2000). "Ikaros interactions with CtBP reveal a repression mechanism that is independent of histone deacetylase activity". J. Biol. Chem. (UNITED STATES) 275 (26): 19594–602. doi:10.1074/jbc.M000254200. ISSN 0021-9258. PMID 10766745.

[1]

[2]

[3]

[4]

[5]

[6]

[7]

[8]

[9]

[10]

[11]

[12]

[13]

[14]

[15]

[16]

[17]

Nov	DEC	Jan
	26
2010	2011	2012

IKZF1

Contents

[edit] Interactions

[edit] References

[edit] Further reading

[edit] External links

Personal tools

Namespaces

Variants

Views

Actions

Search

Navigation

Interaction

Toolbox

Print/export

Languages