Factor de transcripción asociado con microftalmia

Factor de transcripción asociado con microftalmia
HUGO	7105
Símbolo	MITF
Símbolos alt.	WS2A
Datos genéticos
Locus	Cr. 3 p14.1
Bases de datos
Entrez	4286
OMIM	156845
RefSeq	NP_000239
UniProt	O75030

El factor de transcripción asociado con microftalmia (MITF) es un factor de transcripción con un dominio hélice-bucle-hélice básico de cremallera de leucina implicado en el desarrollo de melanocitos^[1] y osteoclastos.^[2]

Importancia clínica

El factor de transcripción MITF podría estar asociado con el síndrome de Tietz^[3] y con el síndrome de Waardenburg tipo IIa.^[4]

Genes diana

La proteína MITF reconoce las secuencias E-box (5'-CANNTG-3') y M-box (5'-TCANNTG-3' ó 5'-CANNTGA-3') en las regiones promotoras de los genes diana (donde C = citosina; A = adenina; T = timina; G = guanina; N = cualquier nucleótido). Entre los genes diana conocidos y confirmados al menos por dos fuentes independientes de este factor de transcripción, se encuentran los siguientes:

ACP5[5] [6]	BCL2[6] [7]	BEST1[6] [8]	BIRC7[6] [9]
Cdk2[6] [10]	CLCN7[6] [11]	DCT[6] [12]	EDNRB[6] [13]
GPNMB[6] [14]	GPR143[6] [15]	MC1R[6] [16]	MLANA[6] [17]
OSTM1[6] [11]	RAB27A[6] [18]	SILV[6] [17]	SLC45A2[6] [19]
TBX2[6] [20]	TRPM1[6] [21]	TYR[6] [22]	TYRP1[6] [23]

Otros genes identificados por estudios de microarrays (que confirmaron las dianas mostradas anteriormente) incluyen los siguientes:^[6]

MBP	TNFRSF14	IRF4	RBM35A
PLA1A	APOLD1	KCNN2	INPP4B
CAPN3	LGALS3	GREB1	FRMD4B
SLC1A4	TBC1D16	GMPR	ASAH1
MICAL1	TMC6	ITPKB	SLC7A8

Interacciones

La proteína MITF ha demostrado ser capaz de interaccionar con:

• PATZ1^[24]
• PIAS3^[25]
• TFE3^{[26] [27]}
• UBE2I^[28]
• LEF1^[12]

Véase también

• Microftalmia

Referencias

1. ↑ Levy C, Khaled M, Fisher DE (2006). «MITF: master regulator of melanocyte development and melanoma oncogene». Trends Mol Med 12 (9):  pp. 406–14. doi:10.1016/j.molmed.2006.07.008. PMID 16899407. 
2. ↑ Hershey CL, Fisher DE (2004). «Mitf and Tfe3: members of a b-HLH-ZIP transcription factor family essential for osteoclast development and function». Bone 34 (4):  pp. 689–96. doi:10.1016/j.bone.2003.08.014. PMID 15050900. 
3. ↑ Smith SD, Kelley PM, Kenyon JB, Hoover D (2000). «Tietz syndrome (hypopigmentation/deafness) caused by mutation of MITF». J. Med. Genet. 37 (6):  pp. 446–8. doi:10.1136/jmg.37.6.446. PMID 10851256. 
4. ↑ Tachibana M, Kobayashi Y, Matsushima Y (2003). «Mouse models for four types of Waardenburg syndrome». Pigment Cell Res. 16 (5):  pp. 448–54. doi:10.1034/j.1600-0749.2003.00066.x. PMID 12950719. 
5. ↑ Luchin A, Purdom G, Murphy K, et al. (2000). «The microphthalmia transcription factor reulates expression of the tartrate-resistant acid phosphatase gene during terminal differentiation of osteoclasts». J. Bone Miner. Res. 15 (3):  pp. 451–460. doi:10.1359/jbmr.2000.15.3.451. PMID 10750559. 
6. ↑ ^{a b c d e f g h i j k l m n ñ o p q r s t} Hoek KS, Schlegel NC, Eichhoff OM, et al. (2008). «Novel MITF targets identified using a two-step DNA microarray strategy». Pigment Cell Melanoma Res. 21 (6):  pp. 665–76. doi:10.1111/j.1755-148X.2008.00505.x. PMID 19067971. 
7. ↑ McGill GG, Horstmann M, Widlund HR, et al. (2002). «Bcl2 regulation by the melanocyte master regulator Mitf modulates lineage survival and melanoma cell viability». Cell 109 (6):  pp. 707–18. doi:10.1016/S0092-8674(02)00762-6. PMID 12086670. 
8. ↑ Esumi N, Kachi S, Campochiaro PA, et al. (2007). «VMD2 promoter requires two proximal E-box sites for its activity in vivo and is regulated by the MITF-TFE family». J. Biol. Chem. 282 (3):  pp. 1838–50. doi:10.1074/jbc.M609517200. PMID 17085443. 
9. ↑ Dynek JN, Chan SM, Liu J, et al. (2008). «Microphthalmia-associated transcription factor is a critical transcriptional regulator of melanoma inhibitor of apoptosis in melanomas». Cancer Res. 68 (9):  pp. 3124–32. doi:10.1158/0008-5472.CAN-07-6622. PMID 18451137. 
10. ↑ Du J, Widlund HR, Horstmann MA, et al. (2004). «Critical role of CDK2 for melanoma growth linked to its melanocyte-specific transcriptional regulation by MITF». Cancer Cell 6 (6):  pp. 565–76. doi:10.1016/j.ccr.2004.10.014. PMID 15607961. 
11. ↑ ^{a b} Meadows NA, Sharma SM, Faulkner GJ, et al. (2007). «The expression of Clcn7 and Ostm1 in osteoclasts is coregulated by microphthalmia transcription factor». J. Biol. Chem. 282 (3):  pp. 1891–904. doi:10.1074/jbc.M608572200. PMID 17105730. 
12. ↑ ^{a b} Yasumoto K, Takeda K, Saito H, et al. (2002). «Microphthalmia-associated transcription factor interacts with LEF-1, a mediator of Wnt signaling». Embo J. 21 (11):  pp. 2703–14. doi:10.1093/emboj/21.11.2703. PMID 12032083. 
13. ↑ Sato-Jin K, Nishimura EK, Akasaka E, et al. (2008). «Epistatic connections between microphthalmia-associated transcription factor and endothelin signaling in Waardenburg syndrome and other pigmentary disorders». Faseb J. 22 (4):  pp. 1155–68. doi:10.1096/fj.07-9080com. PMID 18039926. 
14. ↑ Loftus SK, Antonellis A, Matera I, et al. (2009). «Gpnmb is a Melanoblast-Expressed, MITF-Dependent Gene». Pigment Cell Melanoma Res. 22 (1):  pp. 99. doi:10.1111/j.1755-148X.2008.00518.x. PMID 18983539. 
15. ↑ Vetrini F, Auricchio A, Du J, Angeletti B, et al. (2004). «The microphthalmia transcription factor (Mitf) controls expression of the ocular albinism type 1 gene: link between melanin synthesis and melanosome biogenesis». Mol. Cell Biol. 24 (15):  pp. 6550–9. doi:10.1128/MCB.24.15.6550-6559.2004. PMID 15254223. 
16. ↑ Aoki H, Moro O (2002). «Involvement of microphthalmia-associated transcription factor (MITF) in expression of human melanocortin-1 receptor (MC1R)». Life Sci. 71 (18):  pp. 2171–9. doi:10.1016/S0024-3205(02)01996-3. PMID 12204775. 
17. ↑ ^{a b} Du J, Miller AJ, Widlund HR, et al. (2003). «MLANA/MART1 and SILV/PMEL17/GP100 are transcriptionally regulated by MITF in melanocytes and melanoma». Am. J. Pathol. 163 (1):  pp. 333–43. PMID 12819038. 
18. ↑ Chiaverini C, Beuret L, Flori E, et al. (2008). «Microphthalmia-associated transcription factor regulates RAB27A gene expression and controls melanosome transport». J. Biol. Chem. 283 (18):  pp. 12635–42. doi:10.1074/jbc.M800130200. PMID 18281284. 
19. ↑ Du J, Fisher DE (2002). «Identification of Aim-1 as the underwhite mouse mutant and its transcriptional regulation by MITF». J. Biol. Chem. 277 (1):  pp. 402–6. doi:10.1074/jbc.M110229200. PMID 11700328. 
20. ↑ Carreira S, Liu B, Goding CR (2000). «The gene encoding the T-box factor Tbx2 is a target for the microphthalmia-associated transcription factor in melanocytes». J. Biol. Chem. 275 (29):  pp. 21920–7. doi:10.1074/jbc.M000035200. PMID 10770922. 
21. ↑ Miller AJ, Du J, Rowan S, et al. (2004). «Transcriptional regulation of the melanoma prognostic marker melastatin (TRPM1) by MITF in melanocytes and melanoma». Cancer Res. 64 (2):  pp. 509–16. doi:10.1158/0008-5472.CAN-03-2440. PMID 14744763. 
22. ↑ Hou L, Panthier JJ, Arnheiter H (2000). «Signaling and transcriptional regulation in the neural crest-derived melanocyte lineage: interactions between KIT and MITF». Development 127 (24):  pp. 5379–89. PMID 11076759. 
23. ↑ Fang D, Tsuji Y, Setaluri V (2002). «Selective down-regulation of tyrosinase family gene TYRP1 by inhibition of the activity of melanocyte transcription factor, MITF». Nucleic Acids Res. 30 (14):  pp. 3096–106. doi:10.1093/nar/gkf424. PMID 12136092. 
24. ↑ Morii, Eiichi; Oboki Keisuke, Kataoka Tatsuki R, Igarashi Kazuhiko, Kitamura Yukihiko (Mar. 2002). «Interaction and cooperation of mi transcription factor (MITF) and myc-associated zinc-finger protein-related factor (MAZR) for transcription of mouse mast cell protease 6 gene». J. Biol. Chem. (United States) 277 (10):  pp. 8566–71. doi:10.1074/jbc.M110392200. ISSN 0021-9258. PMID 11751862. 
25. ↑ Levy, Carmit; Nechushtan Hovav, Razin Ehud (Jan. 2002). «A new role for the STAT3 inhibitor, PIAS3: a repressor of microphthalmia transcription factor». J. Biol. Chem. (United States) 277 (3):  pp. 1962–6. doi:10.1074/jbc.M109236200. ISSN 0021-9258. PMID 11709556. 
26. ↑ Steingrimsson, Eiríkur; Tessarollo Lino, Pathak Bhavani, Hou Ling, Arnheiter Heinz, Copeland Neal G, Jenkins Nancy A (Apr. 2002). «Mitf and Tfe3, two members of the Mitf-Tfe family of bHLH-Zip transcription factors, have important but functionally redundant roles in osteoclast development». Proc. Natl. Acad. Sci. U.S.A. (United States) 99 (7):  pp. 4477–82. doi:10.1073/pnas.072071099. ISSN 0027-8424. PMID 11930005. 
27. ↑ Mansky, Kim C; Sulzbacher Sabine, Purdom Georgia, Nelsen Lori, Hume David A, Rehli Michael, Ostrowski Michael C (Feb. 2002). «The microphthalmia transcription factor and the related helix-loop-helix zipper factors TFE-3 and TFE-C collaborate to activate the tartrate-resistant acid phosphatase promoter». J. Leukoc. Biol. (United States) 71 (2):  pp. 304–10. ISSN 0741-5400. PMID 11818452. 
28. ↑ Xu, W; Gong L, Haddad M M, Bischof O, Campisi J, Yeh E T, Medrano E E (Mar. 2000). «Regulation of microphthalmia-associated transcription factor MITF protein levels by association with the ubiquitin-conjugating enzyme hUBC9». Exp. Cell Res. (UNITED STATES) 255 (2):  pp. 135–43. doi:10.1006/excr.2000.4803. ISSN 0014-4827. PMID 10694430. 

Enlaces externos

• MeSH Microphthalmia-associated+transcription+factor