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Ikzf1

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Ikzf1

IKAROS family zinc finger 1 (Ikaros)
Identifiers
Symbols  ; Hs.54452; IK1; IKAROS; LYF1; LyF-1; PPP1R92; PRO0758; ZNFN1A1
External IDs GeneCards:
RNA expression pattern
Orthologs
Species Human Mouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)
RefSeq (protein)
Location (UCSC)
PubMed 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] 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

IKZF1 has been shown to interact with IKZF2,[10] IKZF3,[11][12][13] IKZF4,[14][15] Histone deacetylase 5,[16] HDAC1,[12][16] HDAC7A,[16] SIN3B,[12][16] SIN3A,[12][16][17] and CTBP1.[18]

References

  1. ^ Georgopoulos K, Moore DD, Derfler B (December 1992). "Ikaros, an early lymphoid-specific transcription factor and a putative mediator for T cell commitment". Science 258 (5083): 808–12.  
  2. ^ Hahm K, Ernst P, Lo K, Kim GS, Turck C, Smale ST (November 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.  
  3. ^ "Entrez Gene: IKZF1 IKAROS family zinc finger 1 (Ikaros)". 
  4. ^ a b Kastner P, Chan S (June 2011). "Role of Ikaros in T-cell acute lymphoblastic leukemia". World J Biol Chem 2 (6): 108–14.  
  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; Bloodomics Consortium. (May 2009). "A HaemAtlas: characterizing gene expression in differentiated human blood cells". Blood 113 (19): e1–9.  
  6. ^ Georgopoulos K, Winandy S, Avitahl N. (1997). "The role of the Ikaros gene in lymphocyte development and homeostasis.". Ann Rev Immunol. 15: 155–76.  
  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.  
  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. (September 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.  
  9. ^ a b Swafford AD, Howson JM, Davison LJ, Wallace C, Smyth DJ, Schuilenburg H, Maisuria-Armer M, Mistry T, Lenardo MJ, Todd JA. (February 2011). "An allele of IKZF1 (Ikaros) conferring susceptibility to childhood acute lymphoblastic leukemia protects against type 1 diabetes.". Diabetes 60 (3): 1041–4.  
  10. ^ Kelley CM, Ikeda T, Koipally J, Avitahl N, Wu L, Georgopoulos K, Morgan BA. (April 1998). "Helios, a novel dimerization partner of Ikaros expressed in the earliest hematopoietic progenitors". Curr Biol 8 (9): 508–915.  
  11. ^ Morgan B, Sun L, Avitahl N, Andrikopoulos K, Ikeda T, Gonzales E, Wu P, Neben S, Georgopoulos K. (April 1997). "Aiolos, a lymphoid restricted transcription factor that interacts with Ikaros to regulate lymphocyte differentiation.". EMBO 16 (8): 2004–13.  
  12. ^ a b c d Koipally J, Renold A, Kim J, Georgopoulos K. (June 1999). "Repression by Ikaros and Aiolos is mediated through histone deacetylase complexes.". EMBO 18 (11): 3090–100.  
  13. ^ Kim J, Sif S, Jones B, Jackson A, Koipally J, Heller E, Winandy S, Viel A, Sawyer A, Ikeda T, Kingston R, Georgopoulos K. (March 1999). "Ikaros DNA-binding proteins direct formation of chromatin remodeling complexes in lymphocytes.". Immunity 10 (3): 345–55.  
  14. ^ 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 (March 1999). "Eos: a novel member of the Ikaros gene family expressed predominantly in the developing nervous system". FEBS Lett. (NETHERLANDS) 447 (1): 76–80.  
  15. ^ Perdomo, J; Holmes M; Chong B; Crossley M (December 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.  
  16. ^ a b c d e Koipally, Joseph; Georgopoulos Katia (August 2002). "A molecular dissection of the repression circuitry of Ikaros". J. Biol. Chem. (United States) 277 (31): 27697–705.  
  17. ^ Koipally, Joseph; Georgopoulos Katia (June 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.  
  18. ^ Koipally, J; Georgopoulos K (June 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.  

Further reading

External links


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