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''MAX'' (also known as myc-associated factor X) is a
gene In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...
that in humans encodes the MAX
transcription factor In molecular biology, a transcription factor (TF) (or sequence-specific DNA-binding factor) is a protein that controls the rate of transcription (genetics), transcription of genetics, genetic information from DNA to messenger RNA, by binding t ...
.


Function

The protein product of ''MAX'' contains the
basic helix-loop-helix Basic or BASIC may refer to: Science and technology * BASIC, a computer programming language * Basic (chemistry), having the properties of a base * Basic access authentication, in HTTP Entertainment * ''Basic'' (film), a 2003 film * Basic, one ...
and
leucine zipper A leucine zipper (or leucine scissors) is a common three-dimensional structural motif in proteins. They were first described by Landschulz and collaborators in 1988 when they found that an enhancer binding protein had a very characteristic 30-amin ...
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 An E-box (enhancer box) is a Response element, DNA response element found in some eukaryotes that acts as a protein-binding site and has been found to regulate gene expression in neurons, muscles, and other tissues. Its specific DNA sequence, CANNT ...
) 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. Transcriptionally active hetero- and homodimers involving Max can promote
cell proliferation Cell proliferation is the process by which ''a cell grows and divides to produce two daughter cells''. Cell proliferation leads to an exponential increase in cell number and is therefore a rapid mechanism of tissue growth. Cell proliferation ...
as well as
apoptosis Apoptosis (from ) is a form of programmed cell death that occurs in multicellular organisms and in some eukaryotic, single-celled microorganisms such as yeast. Biochemistry, Biochemical events lead to characteristic cell changes (Morphology (biol ...
.


Interactions

The protein product of Max has been shown to interact with: * Myc, * MNT, * MSH2, *
MXD1 MAD protein is a protein that in humans is encoded by the ''MXD1'' gene. MAD-MAX dimerization protein belongs to a subfamily of MAX-interacting proteins. This protein competes with MYC for binding to MAX to form a sequence-specific DNA-binding c ...
, * MXI1, * MYCL1, * N-Myc, * SPAG9, * TEAD1, and * Transformation/transcription domain-associated protein.


Clinical relevance

This gene has been shown mutated in cases of hereditary
pheochromocytoma Pheochromocytoma is a rare tumor of the adrenal medulla composed of chromaffin cells and is part of the paraganglioma (PGL) family of tumors, being defined as an intra-adrenal PGL. These neuroendocrine tumors can be sympathetic, where they relea ...
. 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.


References


Further reading

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External links

* * {{Transcription factors, g1 Transcription factors