IKZF3 explained

Zinc finger protein Aiolos also known as Ikaros family zinc finger protein 3 is a protein that in humans is encoded by the IKZF3 gene.^{[1] [2] [3]}

Function

This gene encodes a member of the Ikaros family of zinc-finger proteins. Three members of this protein family (Ikaros, Aiolos and Helios) are hematopoietic-specific transcription factors involved in the regulation of lymphocyte development. This gene product is a transcription factor that is important in the regulation of B lymphocyte proliferation and differentiation. Both Ikaros and Aiolos can participate in chromatin remodeling. Regulation of gene expression in B lymphocytes by Aiolos is complex as it appears to require the sequential formation of Ikaros homodimers, Ikaros/Aiolos heterodimers, and Aiolos homodimers. At least six alternative transcripts encoding different isoforms have been described.^[3]

Interactions

IKZF3 has been shown to interact with BCL2-like 1^[4] and HRAS.^[5]

Further reading

• Sun J, Matthias G, Mihatsch MJ, Georgopoulos K, Matthias P . Lack of the transcriptional coactivator OBF-1 prevents the development of systemic lupus erythematosus-like phenotypes in Aiolos mutant mice . Journal of Immunology . 170 . 4 . 1699–706 . February 2003 . 12574333 . 10.4049/jimmunol.170.4.1699 . 31136931 .
• Schmitt C, Tonnelle C, Dalloul A, Chabannon C, Debré P, Rebollo A . Aiolos and Ikaros: regulators of lymphocyte development, homeostasis and lymphoproliferation . Apoptosis . 7 . 3 . 277–84 . June 2002 . 11997672 . 10.1023/A:1015372322419 . 1318582 .
• Wang JH, Avitahl N, Cariappa A, Friedrich C, Ikeda T, Renold A, Andrikopoulos K, Liang L, Pillai S, Morgan BA, Georgopoulos K . Aiolos regulates B cell activation and maturation to effector state . Immunity . 9 . 4 . 543–53 . October 1998 . 9806640 . 10.1016/S1074-7613(00)80637-8 . free .
• Kim J, Sif S, Jones B, Jackson A, Koipally J, Heller E, Winandy S, Viel A, Sawyer A, Ikeda T, Kingston R, Georgopoulos K . Ikaros DNA-binding proteins direct formation of chromatin remodeling complexes in lymphocytes . Immunity . 10 . 3 . 345–55 . March 1999 . 10204490 . 10.1016/S1074-7613(00)80034-5 . free .
• Koipally J, Renold A, Kim J, Georgopoulos K . Repression by Ikaros and Aiolos is mediated through histone deacetylase complexes . The EMBO Journal . 18 . 11 . 3090–100 . June 1999 . 10357820 . 1171390 . 10.1093/emboj/18.11.3090 .
• Romero F, Martínez-A C, Camonis J, Rebollo A . Aiolos transcription factor controls cell death in T cells by regulating Bcl-2 expression and its cellular localization . The EMBO Journal . 18 . 12 . 3419–30 . June 1999 . 10369681 . 1171421 . 10.1093/emboj/18.12.3419 .
• Koipally J, Georgopoulos K . Ikaros interactions with CtBP reveal a repression mechanism that is independent of histone deacetylase activity . The Journal of Biological Chemistry . 275 . 26 . 19594–602 . June 2000 . 10766745 . 10.1074/jbc.M000254200 . free .
• Perdomo J, Holmes M, Chong B, Crossley M . 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 . December 2000 . 10978333 . 10.1074/jbc.M005457200 . free .
• Rebollo A, Ayllón V, Fleischer A, Martínez CA, Zaballos A . The association of Aiolos transcription factor and Bcl-xL is involved in the control of apoptosis . Journal of Immunology . 167 . 11 . 6366–73 . December 2001 . 11714801 . 10.4049/jimmunol.167.11.6366 . free .
• Liippo J, Nera KP, Veistinen E, Lähdesmäki A, Postila V, Kimby E, Riikonen P, Hammarström L, Pelkonen J, Lassila O . Both normal and leukemic B lymphocytes express multiple isoforms of the human Aiolos gene . European Journal of Immunology . 31 . 12 . 3469–74 . December 2001 . 11745366 . 10.1002/1521-4141(200112)31:12<3469::AID-IMMU3469>3.0.CO;2-G . 44722991 .
• Nakase K, Ishimaru F, Fujii K, Tabayashi T, Kozuka T, Sezaki N, Matsuo Y, Harada M . Overexpression of novel short isoforms of Helios in a patient with T-cell acute lymphoblastic leukemia . Experimental Hematology . 30 . 4 . 313–7 . April 2002 . 11937265 . 10.1016/S0301-472X(01)00796-2 . free .
• Koipally J, Georgopoulos K . A molecular dissection of the repression circuitry of Ikaros . The Journal of Biological Chemistry . 277 . 31 . 27697–705 . August 2002 . 12015313 . 10.1074/jbc.M201694200 . free .
• Rual JF, Venkatesan K, Hao T, Hirozane-Kishikawa T, Dricot A, Li N, Berriz GF, Gibbons FD, Dreze M, Ayivi-Guedehoussou N, Klitgord N, Simon C, Boxem M, Milstein S, Rosenberg J, Goldberg DS, Zhang LV, Wong SL, Franklin G, Li S, Albala JS, Lim J, Fraughton C, Llamosas E, Cevik S, Bex C, Lamesch P, Sikorski RS, Vandenhaute J, Zoghbi HY, Smolyar A, Bosak S, Sequerra R, Doucette-Stamm L, Cusick ME, Hill DE, Roth FP, Vidal M . Towards a proteome-scale map of the human protein-protein interaction network . Nature . 437 . 7062 . 1173–8 . October 2005 . 16189514 . 10.1038/nature04209 . 2005Natur.437.1173R . 4427026 .
• Antica M, Dubravcic K, Weber I, Raic L, Labar B, Batinic D . A search for a mutation of the Aiolos phosphorylation domain in lymphocytes from patients with leukemia . Haematologica . 92 . 2 . 260–1 . February 2007 . 17296582 . 10.3324/haematol.10753 . free .
• Ghadiri A, Duhamel M, Fleischer A, Reimann A, Dessauge F, Rebollo A . Critical function of Ikaros in controlling Aiolos gene expression . FEBS Letters . 581 . 8 . 1605–16 . April 2007 . 17383641 . 10.1016/j.febslet.2007.03.025 . 10676033 . free .
• Caballero R, Setien F, Lopez-Serra L, Boix-Chornet M, Fraga MF, Ropero S, Megias D, Alaminos M, Sanchez-Tapia EM, Montoya MC, Esteller M, Gonzalez-Sarmiento R, Ballestar E . Combinatorial effects of splice variants modulate function of Aiolos . Journal of Cell Science . 120 . Pt 15 . 2619–30 . August 2007 . 17646674 . 10.1242/jcs.007344 . free . 10668/612 . free .

Notes and References

1. Morgan B, Sun L, Avitahl N, Andrikopoulos K, Ikeda T, Gonzales E, Wu P, Neben S, Georgopoulos K . Aiolos, a lymphoid restricted transcription factor that interacts with Ikaros to regulate lymphocyte differentiation . The EMBO Journal . 16 . 8 . 2004–13 . April 1997 . 9155026 . 1169803 . 10.1093/emboj/16.8.2004 .
2. Hosokawa Y, Maeda Y, Takahashi EI, Suzuki M, Seto M . Human aiolos, an ikaros-related zinc finger DNA binding protein: cDNA cloning, tissue expression pattern, and chromosomal mapping . Genomics . 61 . 3 . 326–9 . November 1999 . 10552935 . 10.1006/geno.1999.5949 .
3. Web site: Entrez Gene: IKZF3 IKAROS family zinc finger 3 (Aiolos).
4. Rebollo A, Ayllón V, Fleischer A, Martínez CA, Zaballos A . The association of Aiolos transcription factor and Bcl-xL is involved in the control of apoptosis . Journal of Immunology . 167 . 11 . 6366–73 . December 2001 . 11714801 . 10.4049/jimmunol.167.11.6366 . free .
5. Romero F, Martínez-A C, Camonis J, Rebollo A . Aiolos transcription factor controls cell death in T cells by regulating Bcl-2 expression and its cellular localization . The EMBO Journal . 18 . 12 . 3419–30 . June 1999 . 10369681 . 1171421 . 10.1093/emboj/18.12.3419 .