MAX (gene)

Last updated
MAX
1an2 max dimer2.png
Available structures
PDB Ortholog search: PDBe RCSB
Identifiers
Aliases MAX , bHLHd4, max, MYC associated factor X
External IDs OMIM: 154950 MGI: 96921 HomoloGene: 1786 GeneCards: MAX
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 Mb Chr 12: 76.94 – 76.96 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

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

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. [7]

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

Interactions

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

Clinical relevance

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]

Related Research Articles

Myc is a family of regulator genes and proto-oncogenes that code for transcription factors. The Myc family consists of three related human genes: c-myc (MYC), l-myc (MYCL), and n-myc (MYCN). c-myc was the first gene to be discovered in this family, due to homology with the viral gene v-myc.

N-Myc

N-myc proto-oncogene protein also known as N-Myc or basic helix-loop-helix protein 37 (bHLHe37), is a protein that in humans is encoded by the MYCN gene.

MYC

MYC proto-oncogene, bHLH transcription factor is a protein that in humans is encoded by the MYC gene which is a member of the myc family of transcription factors. The protein contains basic helix-loop-helix (bHLH) structural motif.

E2F1

Transcription factor E2F1 is a protein that in humans is encoded by the E2F1 gene.

SIN3A

Paired amphipathic helix protein Sin3a is a protein that in humans is encoded by the SIN3A gene.

Retinoblastoma-like protein 2

Retinoblastoma-like protein 2 is a protein that in humans is encoded by the RBL2 gene.

ID1

DNA-binding protein inhibitor ID-1 is a protein that in humans is encoded by the ID1 gene.

Retinoblastoma-like protein 1

Retinoblastoma-like 1 (p107), also known as RBL1, is a protein that in humans is encoded by the RBL1 gene.

TFE3

Transcription factor E3 is a protein that in humans is encoded by the TFE3 gene.

MXI1

MAX-interacting protein 1 is a protein that in humans is encoded by the MXI1 gene.

HBP1

HMG-box transcription factor 1, also known as HBP1, is a human protein.

KDM5A

Lysine-specific demethylase 5A is an enzyme that in humans is encoded by the KDM5A gene.

SIN3B

Paired amphipathic helix protein Sin3b is a protein that in humans is encoded by the SIN3B gene.

MYCL

L-myc-1 proto-oncogene protein is a protein that in humans is encoded by the MYCL1 gene.

MXD1

MAD protein is a protein that in humans is encoded by the MXD1 gene.

ELK3

ETS domain-containing protein Elk-3 is a protein that in humans is encoded by the ELK3 gene.

<i>MLX</i> (gene)

Max-like protein X is a protein that in humans is encoded by the MLX gene.

MXD4

Max-interacting transcriptional repressor MAD4 is a protein that in humans is encoded by the MXD4 gene.

MNT (gene)

MNT is a Max-binding protein that is encoded by the MNT gene

MXD3

MAX dimerization protein 3 is a protein that in humans is encoded by the MXD3 gene located on Chromosome 5.

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000125952 - Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000059436 - Ensembl, May 2017
  3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  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.
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  13. 1 2 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. 1 2 3 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. 1 2 3 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. 1 2 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. 1 2 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. 1 2 3 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. 1 2 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. S2CID   16142388.
  20. 1 2 3 4 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. S2CID   13317223.
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  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. S2CID   205357831.
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Further reading

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