Disease relevance of Max

• We also analyzed the effects of Myc and Max ectopic expression on the clonogenic growth of the rat hepatoma cells [1].
• These data support the hypothesis that N-Myc affects neuroblastoma gene expression through the formation of a DNA-binding heterodimeric complex with Max in vivo [2].
• Reintroduction of max into PC12 cells results in repression of E-box-dependent transcription and a reduction in growth rate, which may explain the loss of Max expression either during the growth of the pheochromocytoma or in subsequent passage of the PC12 cell line in vitro [3].

High impact information on Max

• This delta Max protein retained the ability to bind to the CACGTG motif in a complex with c-Myc but lacks the nuclear localization signal and the putative regulatory domain of Max [4].
• When tested in a myc-ras cotransformation assay in rat embryo fibroblasts, Max suppressed, whereas delta Max enhanced, transformation [4].
• Alternative forms of Max as enhancers or suppressors of Myc-ras cotransformation [4].
• Myc heterodimerizes with a partner protein termed Max; the heterodimeric complex binds to CAC(G/A)TG (E-box) sequences and activates transcription from these sites [5].
• The c-Myc protein induces cell cycle progression and apoptosis through dimerization with Max [6].

Biological context of Max

• Myc drives apoptosis in PC12 cells in the absence of Max [7].
• The Myc/Max/Mad network of transcriptional regulatory proteins plays an essential role in cell proliferation, growth, apoptosis, and differentiation [8].
• These results show that Myc can induce apoptosis in PC12 cells in a Max-independent manner and that alternate signaling pathways exist to mediate cell survival [7].
• Nevertheless, treatment of PC-12 cells with NGF and serum caused an increase in the expression of the c-Myc protein and the transcription of a reporter gene linked to the Myc/Max DNA binding site [9].
• Therefore, Myc/Max complexes may not be an absolute requirement for Myc-dependent gene expression [9].

Anatomical context of Max

• Inhibition of endogenous hepatocyte Max levels via expression of an antisense max construct driven by the MMTV promoter did not affect the DNA synthetic response in the presence of dHGF (a variant of HGF) [10].
• Molecular cloning and sequencing of rat Max cDNA: castration-induced expression of the 2 kb transcript in male accessory sex organs of rats [11].
• Transfection of a Max-expressing plasmid into endothelial cells rescued the apoptosis induced by serum deprivation [12].
• Immunoreactivity of the c-Myc dimerization partner Max was mainly in the nucleus of proliferative chondrocytes and decreased as the chondrocytes matured [13].
• We show that in the PC12 pheochromocytoma tumor cell line, functional Max protein is not expressed because of the synthesis of a mutant max transcript [3].

Associations of Max with chemical compounds

• Max activity is affected by phosphorylation at two NH2-terminal sites [14].
• Replacing these serine by alanine residues and comparing the wild type with the mutant Max proteins in transactivation assays did not reveal any significant differences [15].
• In this study, the glucose-mediated induction of L-type pyruvate kinase and glucose-6-phosphatase mRNA levels was diminished by maneuvers involving recombinant adenoviral vectors that interfere with (i) c-Myc protein levels by antisense expression or (ii) c-Myc function through a dominant-negative Max protein [16].

Physical interactions of Max

• Max is a basic-helix-loop-helix-leucine zipper protein capable of forming sequence-specific DNA binding complexes with Myc proteins [4].

Other interactions of Max

• Neutralization with anti-adrenomedullin antiserum or blockade with a CGRP receptor antagonist, CGRP(8-37), reduced Max mRNA levels in growing endothelial cells and enhanced apoptosis after serum starvation [12].
• By using complementary leucine zipper mutants (termed MycEG and MaxEG), which dimerize efficiently with each other but not with their wild-type partners, we demonstrate that both cell cycle progression and apoptosis in nontransformed rodent fibroblasts are induced by Myc-Max dimers [6].

Analytical, diagnostic and therapeutic context of Max

• By means of sequential immunoprecipitation of chromatin using anti-Max and anti-Myc antibodies, we have identified a Myc-regulated gene and genomic sites occupied by Myc-Max in vivo [17].
• In addition to the previously identified Max and delta Max proteins, sequence analysis of a 3.5-kb mRNA form predicted a protein that resembles delta Max in structure [18].

References