MAX (gene)

From Wikipedia, the free encyclopedia
Jump to navigation Jump to search
MAX
1an2 max dimer2.png
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesMAX, bHLHd4, max, MYC associated factor X
External IDsOMIM: 154950 MGI: 96921 HomoloGene: 1786 GeneCards: MAX
Gene location (Human)
Chromosome 14 (human)
Chr.Chromosome 14 (human)[1]
Chromosome 14 (human)
Genomic location for MAX
Genomic location for MAX
Band14q23.3Start65,006,174 bp[1]
End65,102,695 bp[1]
RNA expression pattern
PBB GE MAX 214108 at fs.png

PBB GE MAX 208403 x at fs.png

PBB GE MAX 209331 s at fs.png
More reference expression data
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_001146176
NM_008558
NM_001361663
NM_001361664

RefSeq (protein)

NP_001139648
NP_001348592
NP_001348593
NP_032584

Location (UCSC)Chr 14: 65.01 – 65.1 MbChr 12: 76.94 – 76.96 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

MAX (also known as myc-associated factor X) is a gene that in humans encodes the MAX transcription factor.[5][6]

Function[edit]

The protein product of MAX contains the basic helix-loop-helix and leucine zipper motifs. It is therefore included in the bHLHZ family of transcription factors. It is able to form homodimers with other MAX proteins and heterodimers with other transcription factors, including Mad, Mxl1 and Myc. The homodimers and heterodimers compete for a common DNA target site (the E-box) in a gene promoter zone. Rearrangement of dimers (e.g., Mad:Max, Max:Myc) provides a system of transcriptional regulation with greater diversity of gene targets. Max must dimerise in order to be biologically active.[7]

Transcriptionally active hetero- and homodimers involving Max can promote cell proliferation as well as apoptosis.[8]

Interactions[edit]

The protein product of Max has been shown to interact with:

Clinical relevance[edit]

This gene has been shown mutated in cases of hereditary pheochromocytoma.[25] More recently the Max gene becomes mutated and becomes inactivated in small cell lung cancer (SCLC). This is mutually exclusive with alterations at Myc and BRG1, the latter coding for an ATPase of the SWI/SNF complex. It was demonstrated that the BRG1 product regulates the expression of Max through direct recruitment to the Max promoter region, and that depletion of BRG1 strongly hinders cell growth, specifically in Max-deficient cells, suggesting that the two together cause synthetic lethality. Furthermore, Max required BRG1 to activate neuroendocrine transcriptional programs and to up-regulate Myc targets, such as glycolytic-related genes.[26]

References[edit]

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000125952 - Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000059436 - Ensembl, May 2017
  3. ^ "Human PubMed Reference:".
  4. ^ "Mouse PubMed Reference:".
  5. ^ Wagner AJ, Le Beau MM, Diaz MO, Hay N (May 1992). "Expression, regulation, and chromosomal localization of the Max gene". Proc Natl Acad Sci U S A. 89 (7): 3111–5. Bibcode:1992PNAS...89.3111W. doi:10.1073/pnas.89.7.3111. PMC 48814. PMID 1557420.
  6. ^ "Entrez Gene: MAX MYC associated factor X".
  7. ^ Ecevit, O; Khan, MA; Goss, DJ (30 March 2010). "Kinetic analysis of the interaction of b/HLH/Z transcription factors Myc, Max, and Mad with cognate DNA". Biochemistry. 30 (42): 2627–2635. doi:10.1021/bi901913a. PMC 2852888. PMID 20170194.
  8. ^ Amati B, Land H (February 1994). "Myc-Max-Mad: a transcription factor network controlling cell cycle progression, differentiation and death". Curr. Opin. Genet. Dev. 4 (1): 102–8. doi:10.1016/0959-437X(94)90098-1. PMID 8193530.
  9. ^ Ewing RM, Chu P, Elisma F, Li H, Taylor P, Climie S, McBroom-Cerajewski L, Robinson MD, O'Connor L, Li M, Taylor R, Dharsee M, Ho Y, Heilbut A, Moore L, Zhang S, Ornatsky O, Bukhman YV, Ethier M, Sheng Y, Vasilescu J, Abu-Farha M, Lambert JP, Duewel HS, Stewart II, Kuehl B, Hogue K, Colwill K, Gladwish K, Muskat B, Kinach R, Adams SL, Moran MF, Morin GB, Topaloglou T, Figeys D (2007). "Large-scale mapping of human protein-protein interactions by mass spectrometry". Mol. Syst. Biol. 3: 89. doi:10.1038/msb4100134. PMC 1847948. PMID 17353931.
  10. ^ a b McMahon SB, Wood MA, Cole MD (January 2000). "The essential cofactor TRRAP recruits the histone acetyltransferase hGCN5 to c-Myc". Mol. Cell. Biol. 20 (2): 556–62. doi:10.1128/MCB.20.2.556-562.2000. PMC 85131. PMID 10611234.
  11. ^ a b McMahon SB, Van Buskirk HA, Dugan KA, Copeland TD, Cole MD (August 1998). "The novel ATM-related protein TRRAP is an essential cofactor for the c-Myc and E2F oncoproteins". Cell. 94 (3): 363–74. doi:10.1016/S0092-8674(00)81479-8. PMID 9708738.
  12. ^ Cheng SW, Davies KP, Yung E, Beltran RJ, Yu J, Kalpana GV (May 1999). "c-MYC interacts with INI1/hSNF5 and requires the SWI/SNF complex for transactivation function". Nat. Genet. 22 (1): 102–5. doi:10.1038/8811. PMID 10319872.
  13. ^ a b Mac Partlin M, Homer E, Robinson H, McCormick CJ, Crouch DH, Durant ST, Matheson EC, Hall AG, Gillespie DA, Brown R (February 2003). "Interactions of the DNA mismatch repair proteins MLH1 and MSH2 with c-MYC and MAX". Oncogene. 22 (6): 819–25. doi:10.1038/sj.onc.1206252. PMID 12584560.
  14. ^ a b c Blackwood EM, Eisenman RN (Mar 1991). "Max: a helix-loop-helix zipper protein that forms a sequence-specific DNA-binding complex with Myc". Science. 251 (4998): 1211–7. Bibcode:1991Sci...251.1211B. doi:10.1126/science.2006410. ISSN 0036-8075. PMID 2006410.
  15. ^ a b c Lee CM, Onésime D, Reddy CD, Dhanasekaran N, Reddy EP (October 2002). "JLP: A scaffolding protein that tethers JNK/p38MAPK signaling modules and transcription factors". Proc. Natl. Acad. Sci. U.S.A. 99 (22): 14189–94. Bibcode:2002PNAS...9914189L. doi:10.1073/pnas.232310199. PMC 137859. PMID 12391307.
  16. ^ a b Billin AN, Eilers AL, Queva C, Ayer DE (December 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. PMID 10593926.
  17. ^ a b Gupta K, Anand G, Yin X, Grove L, Prochownik EV (March 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. PMID 9528857.
  18. ^ a b c Meroni G, Reymond A, Alcalay M, Borsani G, Tanigami A, Tonlorenzi R, Lo Nigro C, Messali S, Zollo M, Ledbetter DH, Brent R, Ballabio A, Carrozzo R (May 1997). "Rox, a novel bHLHZip protein expressed in quiescent cells that heterodimerizes with Max, binds a non-canonical E box and acts as a transcriptional repressor". EMBO J. 16 (10): 2892–906. doi:10.1093/emboj/16.10.2892. PMC 1169897. PMID 9184233.
  19. ^ a b Nair SK, Burley SK (January 2003). "X-ray structures of Myc-Max and Mad-Max recognizing DNA. Molecular bases of regulation by proto-oncogenic transcription factors". Cell. 112 (2): 193–205. doi:10.1016/S0092-8674(02)01284-9. PMID 12553908.
  20. ^ a b c d FitzGerald MJ, Arsura M, Bellas RE, Yang W, Wu M, Chin L, Mann KK, DePinho RA, Sonenshein GE (April 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. PMID 10229200.
  21. ^ Meroni G, Cairo S, Merla G, Messali S, Brent R, Ballabio A, Reymond A (July 2000). "Mlx, a new Max-like bHLHZip family member: the center stage of a novel transcription factors regulatory pathway?". Oncogene. 19 (29): 3266–77. doi:10.1038/sj.onc.1203634. PMID 10918583.
  22. ^ Ayer DE, Kretzner L, Eisenman RN (January 1993). "Mad: a heterodimeric partner for Max that antagonizes Myc transcriptional activity". Cell. 72 (2): 211–22. doi:10.1016/0092-8674(93)90661-9. PMID 8425218.
  23. ^ 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 (October 2005). "Towards a proteome-scale map of the human protein-protein interaction network". Nature. 437 (7062): 1173–8. Bibcode:2005Natur.437.1173R. doi:10.1038/nature04209. PMID 16189514.
  24. ^ Gupta MP, Amin CS, Gupta M, Hay N, Zak R (July 1997). "Transcription enhancer factor 1 interacts with a basic helix-loop-helix zipper protein, Max, for positive regulation of cardiac alpha-myosin heavy-chain gene expression". Mol. Cell. Biol. 17 (7): 3924–36. doi:10.1128/mcb.17.7.3924. PMC 232245. PMID 9199327.
  25. ^ Comino-Méndez I, Gracia-Aznárez FJ, Schiavi F, Landa I, Leandro-García LJ, Letón R, Honrado E, Ramos-Medina R, Caronia D, Pita G, Gómez-Graña A, de Cubas AA, Inglada-Pérez L, Maliszewska A, Taschin E, Bobisse S, Pica G, Loli P, Hernández-Lavado R, Díaz JA, Gómez-Morales M, González-Neira A, Roncador G, Rodríguez-Antona C, Benítez J, Mannelli M, Opocher G, Robledo M, Cascón A (July 2011). "Exome sequencing identifies MAX mutations as a cause of hereditary pheochromocytoma". Nat. Genet. 43 (7): 663–7. doi:10.1038/ng.861. PMID 21685915.
  26. ^ Romero OA, Torres-Diz M, Pros E, Savola S, Gomez A, Moran S, Saez C, Iwakawa R, Villanueva A, Montuenga LM, Kohno T, Yokota J, Sanchez-Cespedes M (Dec 2013). "MAX inactivation in small-cell lung cancer disrupts the MYC-SWI/SNF programs and is synthetic lethal with BRG1". Cancer Discov. 4 (3): 292–303. doi:10.1158/2159-8290.CD-13-0799. PMID 24362264.

Further reading[edit]

External links[edit]

This article incorporates text from the United States National Library of Medicine, which is in the public domain.