Biology:MAX (gene)
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Short description: Protein-coding gene in the species Homo sapiens
 Generic protein structure example |
MAX (also known as myc-associated factor X) is a gene that in humans encodes the MAX transcription factor.[1][2]
Function
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.[3]
Transcriptionally active hetero- and homodimers involving Max can promote cell proliferation as well as apoptosis.[4]
Interactions
The protein product of Max has been shown to interact with:
- Myc,[5][6][7][8][9][10][11][12][13][14][15][16][17]
- MNT,[14]
- MSH2,[9]
- MXD1,[11][13][15][18]
- MXI1,[12][14][16][19]
- MYCL1,[10][16]
- N-Myc,[10][16]
- SPAG9,[11]
- TEAD1,[20] and
- Transformation/transcription domain-associated protein.[6][7]
Clinical relevance
This gene has been shown mutated in cases of hereditary pheochromocytoma.[21] 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.[22]
References
- ↑ "Expression, regulation, and chromosomal localization of the Max gene". Proc Natl Acad Sci U S A 89 (7): 3111–5. May 1992. doi:10.1073/pnas.89.7.3111. PMID 1557420. Bibcode: 1992PNAS...89.3111W.
- ↑ "Entrez Gene: MAX MYC associated factor X". https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=4149.
- ↑ 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. PMID 20170194.
- ↑ "Myc-Max-Mad: a transcription factor network controlling cell cycle progression, differentiation and death". Curr. Opin. Genet. Dev. 4 (1): 102–8. February 1994. doi:10.1016/0959-437X(94)90098-1. PMID 8193530.
- ↑ "Large-scale mapping of human protein-protein interactions by mass spectrometry". Mol. Syst. Biol. 3: 89. 2007. doi:10.1038/msb4100134. PMID 17353931.
- ↑ 6.0 6.1 "The essential cofactor TRRAP recruits the histone acetyltransferase hGCN5 to c-Myc". Mol. Cell. Biol. 20 (2): 556–62. January 2000. doi:10.1128/MCB.20.2.556-562.2000. PMID 10611234.
- ↑ 7.0 7.1 "The novel ATM-related protein TRRAP is an essential cofactor for the c-Myc and E2F oncoproteins". Cell 94 (3): 363–74. August 1998. doi:10.1016/S0092-8674(00)81479-8. PMID 9708738.
- ↑ "c-MYC interacts with INI1/hSNF5 and requires the SWI/SNF complex for transactivation function". Nat. Genet. 22 (1): 102–5. May 1999. doi:10.1038/8811. PMID 10319872.
- ↑ 9.0 9.1 "Interactions of the DNA mismatch repair proteins MLH1 and MSH2 with c-MYC and MAX". Oncogene 22 (6): 819–25. February 2003. doi:10.1038/sj.onc.1206252. PMID 12584560.
- ↑ 10.0 10.1 10.2 "Max: a helix-loop-helix zipper protein that forms a sequence-specific DNA-binding complex with Myc". Science 251 (4998): 1211–7. Mar 1991. doi:10.1126/science.2006410. ISSN 0036-8075. PMID 2006410. Bibcode: 1991Sci...251.1211B.
- ↑ 11.0 11.1 11.2 "JLP: A scaffolding protein that tethers JNK/p38MAPK signaling modules and transcription factors". Proc. Natl. Acad. Sci. U.S.A. 99 (22): 14189–94. October 2002. doi:10.1073/pnas.232310199. PMID 12391307. Bibcode: 2002PNAS...9914189L.
- ↑ 12.0 12.1 "Mlx, a novel Max-like BHLHZip protein that interacts with the Max network of transcription factors". J. Biol. Chem. 274 (51): 36344–50. December 1999. doi:10.1074/jbc.274.51.36344. PMID 10593926.
- ↑ 13.0 13.1 "Mmip1: a novel leucine zipper protein that reverses the suppressive effects of Mad family members on c-myc". Oncogene 16 (9): 1149–59. March 1998. doi:10.1038/sj.onc.1201634. PMID 9528857.
- ↑ 14.0 14.1 14.2 "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. May 1997. doi:10.1093/emboj/16.10.2892. PMID 9184233.
- ↑ 15.0 15.1 "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. January 2003. doi:10.1016/S0092-8674(02)01284-9. PMID 12553908.
- ↑ 16.0 16.1 16.2 16.3 "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. April 1999. doi:10.1038/sj.onc.1202611. PMID 10229200.
- ↑ "Mlx, a new Max-like bHLHZip family member: the center stage of a novel transcription factors regulatory pathway?". Oncogene 19 (29): 3266–77. July 2000. doi:10.1038/sj.onc.1203634. PMID 10918583.
- ↑ "Mad: a heterodimeric partner for Max that antagonizes Myc transcriptional activity". Cell 72 (2): 211–22. January 1993. doi:10.1016/0092-8674(93)90661-9. PMID 8425218.
- ↑ "Towards a proteome-scale map of the human protein-protein interaction network". Nature 437 (7062): 1173–8. October 2005. doi:10.1038/nature04209. PMID 16189514. Bibcode: 2005Natur.437.1173R.
- ↑ "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. July 1997. doi:10.1128/mcb.17.7.3924. PMID 9199327.
- ↑ "Exome sequencing identifies MAX mutations as a cause of hereditary pheochromocytoma". Nat. Genet. 43 (7): 663–7. July 2011. doi:10.1038/ng.861. PMID 21685915.
- ↑ "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. Dec 2013. doi:10.1158/2159-8290.CD-13-0799. PMID 24362264.
Further reading
- "The Myc/Max/Mad network and the transcriptional control of cell behavior.". Annu. Rev. Cell Dev. Biol. 16: 653–99. 2001. doi:10.1146/annurev.cellbio.16.1.653. PMID 11031250.
- Lüscher B (2001). "Function and regulation of the transcription factors of the Myc/Max/Mad network.". Gene 277 (1–2): 1–14. doi:10.1016/S0378-1119(01)00697-7. PMID 11602341.
- "Opposite orientations of DNA bending by c-Myc and Max.". Proc. Natl. Acad. Sci. U.S.A. 89 (16): 7635–9. 1992. doi:10.1073/pnas.89.16.7635. PMID 1323849. Bibcode: 1992PNAS...89.7635W.
- "Alternative forms of Max as enhancers or suppressors of Myc-ras cotransformation.". Science 256 (5055): 373–7. 1992. doi:10.1126/science.256.5055.373. PMID 1566084. Bibcode: 1992Sci...256..373M.
- "Mapping of MAX to human chromosome 14 and mouse chromosome 12 by in situ hybridization.". Oncogene 7 (6): 1249–51. 1992. PMID 1594250.
- "Max: a helix-loop-helix zipper protein that forms a sequence-specific DNA-binding complex with Myc.". Science 251 (4998): 1211–7. 1991. doi:10.1126/science.2006410. PMID 2006410. Bibcode: 1991Sci...251.1211B.
- "Mxi2, a mitogen-activated protein kinase that recognizes and phosphorylates Max protein.". Proc. Natl. Acad. Sci. U.S.A. 92 (23): 10531–4. 1995. doi:10.1073/pnas.92.23.10531. PMID 7479834. Bibcode: 1995PNAS...9210531Z.
- "Identification of casein kinase II phosphorylation sites in Max: effects on DNA-binding kinetics of Max homo- and Myc/Max heterodimers.". Oncogene 8 (12): 3211–20. 1993. PMID 8247525.
- "Mad: a heterodimeric partner for Max that antagonizes Myc transcriptional activity.". Cell 72 (2): 211–22. 1993. doi:10.1016/0092-8674(93)90661-9. PMID 8425218.
- "Alternative mRNA forms and open reading frames of the max gene.". Oncogene 8 (2): 503–7. 1993. PMID 8426752.
- "Recognition by Max of its cognate DNA through a dimeric b/HLH/Z domain.". Nature 363 (6424): 38–45. 1993. doi:10.1038/363038a0. PMID 8479534. Bibcode: 1993Natur.363...38F.
- "Mad3 and Mad4: novel Max-interacting transcriptional repressors that suppress c-myc dependent transformation and are expressed during neural and epidermal differentiation.". EMBO J. 14 (22): 5646–59. 1996. doi:10.1002/j.1460-2075.1995.tb00252.x. PMID 8521822.
- "Myc-Max heterodimers activate a DEAD box gene and interact with multiple E box-related sites in vivo.". EMBO J. 15 (16): 4344–57. 1996. doi:10.1002/j.1460-2075.1996.tb00808.x. PMID 8861962.
- "The crystal structure of an intact human Max-DNA complex: new insights into mechanisms of transcriptional control.". Structure 5 (4): 509–20. 1997. doi:10.1016/S0969-2126(97)00207-4. PMID 9115440.
- "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. 1997. doi:10.1093/emboj/16.10.2892. PMID 9184233.
- "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. 1997. doi:10.1128/mcb.17.7.3924. PMID 9199327.
- "Mmip1: a novel leucine zipper protein that reverses the suppressive effects of Mad family members on c-myc.". Oncogene 16 (9): 1149–59. 1998. doi:10.1038/sj.onc.1201634. PMID 9528857.
- "Insights into the mechanism of heterodimerization from the 1H-NMR solution structure of the c-Myc-Max heterodimeric leucine zipper.". J. Mol. Biol. 281 (1): 165–81. 1998. doi:10.1006/jmbi.1998.1914. PMID 9680483.
- "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. 1999. doi:10.1038/sj.onc.1202611. PMID 10229200.
External links
- MAX+protein,+human at the US National Library of Medicine Medical Subject Headings (MeSH)
- FactorBook Max
This article incorporates text from the United States National Library of Medicine, which is in the public domain.
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