Expression of the c-myc gene, which produces an oncogenic transcription factor, is tightly regulated in normal cells but is frequently deregulated in human cancers. The protein encoded by this gene is a transcriptional repressor thought to negatively regulate MYC function, and is therefore a potential tumor suppressor. This protein inhibits the transcriptional activity of MYC by competing for MAX, another basic helix-loop-helix protein that binds to MYC and is required for its function. Defects in this gene are frequently found in patients with prostate tumors. Three alternatively spliced transcripts encoding different isoforms have been described. Additional alternatively spliced transcripts may exist but the products of these transcripts have not been verified experimentally.[2]
↑ 3.03.1Gupta K, Anand G, Yin X, Grove L, Prochownik EV (Mar 1998). "Mmip1: a novel leucine zipper protein that reverses the suppressive effects of Mad family members on c-myc". Oncogene. 16 (9): 1149–59. doi:10.1038/sj.onc.1201634. PMID9528857.
↑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 (Oct 2005). "Towards a proteome-scale map of the human protein-protein interaction network". Nature. 437 (7062): 1173–8. doi:10.1038/nature04209. PMID16189514.
↑Billin AN, Eilers AL, Queva C, Ayer DE (Dec 1999). "Mlx, a novel Max-like BHLHZip protein that interacts with the Max network of transcription factors". J. Biol. Chem. 274 (51): 36344–50. doi:10.1074/jbc.274.51.36344. PMID10593926.
↑FitzGerald MJ, Arsura M, Bellas RE, Yang W, Wu M, Chin L, Mann KK, DePinho RA, Sonenshein GE (Apr 1999). "Differential effects of the widely expressed dMax splice variant of Max on E-box vs initiator element-mediated regulation by c-Myc". Oncogene. 18 (15): 2489–98. doi:10.1038/sj.onc.1202611. PMID10229200.
Further reading
Zervos AS, Gyuris J, Brent R (1993). "Mxi1, a protein that specifically interacts with Max to bind Myc-Max recognition sites". Cell. 72 (2): 223–32. doi:10.1016/0092-8674(93)90662-A. PMID8425219.
Schreiber-Agus N, Meng Y, Hoang T, Hou H, Chen K, Greenberg R, Cordon-Cardo C, Lee HW, DePinho RA (1998). "Role of Mxi1 in ageing organ systems and the regulation of normal and neoplastic growth". Nature. 393 (6684): 483–7. doi:10.1038/31008. PMID9624006.
Eagle LR, Yin X, Brothman AR, Williams BJ, Atkin NB, Prochownik EV (1995). "Mutation of the MXI1 gene in prostate cancer". Nat. Genet. 9 (3): 249–55. doi:10.1038/ng0395-249. PMID7773287.
Albarosa R, DiDonato S, Finocchiaro G (1995). "Redefinition of the coding sequence of the MXI1 gene and identification of a polymorphic repeat in the 3' non-coding region that allows the detection of loss of heterozygosity of chromosome 10q25 in glioblastomas". Hum. Genet. 95 (6): 709–11. doi:10.1007/BF00209493. PMID7789959.
Schreiber-Agus N, Chin L, Chen K, Torres R, Rao G, Guida P, Skoultchi AI, DePinho RA (1995). "An amino-terminal domain of Mxi1 mediates anti-Myc oncogenic activity and interacts with a homolog of the yeast transcriptional repressor SIN3". Cell. 80 (5): 777–86. doi:10.1016/0092-8674(95)90356-9. PMID7889571.
Edelhoff S, Ayer DE, Zervos AS, Steingrímsson E, Jenkins NA, Copeland NG, Eisenman RN, Brent R, Disteche CM (1994). "Mapping of two genes encoding members of a distinct subfamily of MAX interacting proteins: MAD to human chromosome 2 and mouse chromosome 6, and MXI1 to human chromosome 10 and mouse chromosome 19". Oncogene. 9 (2): 665–8. PMID8290278.
Wechsler DS, Shelly CA, Dang CV (1997). "Genomic organization of human MXI1, a putative tumor suppressor gene". Genomics. 32 (3): 466–70. doi:10.1006/geno.1996.0144. PMID8838813.
Bonaldo MF, Lennon G, Soares MB (1997). "Normalization and subtraction: two approaches to facilitate gene discovery". Genome Res. 6 (9): 791–806. doi:10.1101/gr.6.9.791. PMID8889548.
Shimizu E, Shirasawa H, Kodama K, Sato T, Simizu B (1997). "Expression, regulation and polymorphism of the mxi1 genes". Gene. 176 (1–2): 45–8. doi:10.1016/0378-1119(96)00206-5. PMID8918230.
Gupta K, Anand G, Yin X, Grove L, Prochownik EV (1998). "Mmip1: a novel leucine zipper protein that reverses the suppressive effects of Mad family members on c-myc". Oncogene. 16 (9): 1149–59. doi:10.1038/sj.onc.1201634. PMID9528857.
Prochownik EV, Eagle Grove L, Deubler D, Zhu XL, Stephenson RA, Rohr LR, Yin X, Brothman AR (1999). "Commonly occurring loss and mutation of the MXI1 gene in prostate cancer". Genes Chromosomes Cancer. 22 (4): 295–304. doi:10.1002/(SICI)1098-2264(199808)22:4<295::AID-GCC5>3.0.CO;2-Q. PMID9669667.
Li XJ, Wang DY, Zhu Y, Guo RJ, Wang XD, Lubomir K, Mukai K, Sasaki H, Yoshida H, Oka T, Machinami R, Shinmura K, Tanaka M, Sugimura H (1999). "Mxi1 mutations in human neurofibrosarcomas". Jpn. J. Cancer Res. 90 (7): 740–6. doi:10.1111/j.1349-7006.1999.tb00809.x. PMID10470286.
Benson LQ, Coon MR, Krueger LM, Han GC, Sarnaik AA, Wechsler DS (1999). "Expression of MXI1, a Myc antagonist, is regulated by Sp1 and AP2". J. Biol. Chem. 274 (40): 28794–802. doi:10.1074/jbc.274.40.28794. PMID10497252.
Taj MM, Tawil RJ, Engstrom LD, Zeng Z, Hwang C, Sanda MG, Wechsler DS (2001). "Mxi1, a Myc antagonist, suppresses proliferation of DU145 human prostate cells". Prostate. 47 (3): 194–204. doi:10.1002/pros.1063. PMID11351349.
Yin X, Landay MF, Han W, Levitan ES, Watkins SC, Levenson RM, Farkas DL, Prochownik EV (2001). "Dynamic in vivo interactions among Myc network members". Oncogene. 20 (34): 4650–64. doi:10.1038/sj.onc.1204606. PMID11498788.
Ariyanayagam-Baksh SM, Baksh FK, Swalsky PA, Finkelstein SD (2004). "Loss of heterozygosity in the MXI1 gene is a frequent occurrence in melanoma". Mod. Pathol. 16 (10): 992–5. doi:10.1097/01.MP.0000087421.44975.1C. PMID14559981.