Mnt takes control as key regulator of the myc/max/mxd network.
Myc is the most frequently deregulated oncogene in human tumors. The protein belongs to the Myc/Max/Mxd network of transcriptional regulators important for cell growth, proliferation, differentiation, and apoptosis. The ratio between Mnt/Max and c-Myc/Max on the 5'-CACGTG-3' E-box sequence at shared target genes is of great importance for cell cycle progression and arrest. Serum stimulation of quiescent cells results in phosphorylation of Mnt and disruption of the critical Mnt-mSin3-HDAC1 interaction. This in turn leads to increased expression of the Myc/Mnt target gene cyclin D2. It is therefore possible that Myc function relies on its ability to overcome transcriptional repression by Mnt and that relief of Mnt-mediated transcriptional repression is of greater importance for regulation of target genes than the sole activation by Myc. In addition, Mnt has many features of a tumor suppressor and may thus be nonfunctional or inactivated in human tumors. In summary, accumulating evidence supports the model of Mnt as the key regulator of the network in vivo.
Wahlström
Therese
T
Department of Microbiology, Tumor, and Cell Biology (MTC), Karolinska Institutet, SE-171 77 Stockholm, Sweden.
Henriksson
Marie
M
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / Q000037:antagonists & inhibitors / Q000172:deficiency / Q000502:physiology*; D002455:Cell Division; D016503:Drug Delivery Systems; D015972:Gene Expression Regulation, Neoplastic; D053263:Gene Regulatory Networks; D016147:Genes, Tumor Suppressor; D016259:Genes, myc; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors / Q000502:physiology*; D009369:Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism; D016271:Proto-Oncogene Proteins c-myc / Q000502:physiology*; D012097:Repressor Proteins / Q000037:antagonists & inhibitors / Q000502:physiology*; D014158:Transcription, Genetic
D000970:Antineoplastic Agents; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; C499330:MAX protein, human; C106465:MNT protein, human; C079439:MXD1 protein, human; C499479:Mad protein, mouse; C484561:Mnt protein, mouse; D009363:Neoplasm Proteins; D016271:Proto-Oncogene Proteins c-myc; D012097:Repressor Proteins; C068422:Max protein, mouse