The activities of MYC, MNT and the MAX-interactome in lymphocyte proliferation and oncogenesis

• Published in: Biochimica et biophysica acta Vol. 1849; no. 5; pp. 554 - 562
• Main Authors: Link, Jason M., Hurlin, Peter J.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01-05-2015
• Subjects: Apoptosis; B-Lymphocytes - metabolism; Basic Helix-Loop-Helix Leucine Zipper Transcription Factors - biosynthesis; Basic Helix-Loop-Helix Leucine Zipper Transcription Factors - genetics; Basic Helix-Loop-Helix Leucine Zipper Transcription Factors - metabolism; Carcinogenesis - genetics; Carcinogenesis - metabolism; Cell Proliferation - genetics; Gene Expression Regulation, Neoplastic; Humans; Lymphocyte Activation - genetics; Lymphocytes; Lymphoma; Lymphoma - genetics; Lymphoma - metabolism; Lymphoma - pathology; Metabolism; MNT; MYC; Proliferation; Protein Interaction Maps; Proto-Oncogene Proteins c-myc - biosynthesis; Proto-Oncogene Proteins c-myc - metabolism; Repressor Proteins - genetics; Repressor Proteins - metabolism; T-Lymphocytes - metabolism; MNT; Lymphocytes; MYC; Proliferation; Metabolism; Lymphoma; Apoptosis
• ISSN: 1874-9399; 0006-3002; 1876-4320
• DOI: 10.1016/j.bbagrm.2014.04.004

The MYC family of proteins plays essential roles in embryonic development and in oncogenesis. Efforts over the past 30years to define the transcriptional activities of MYC and how MYC functions to promote proliferation have produced evolving models of MYC function. One picture that has emerged of MYC and its partner protein MAX is of a transcription factor complex with a seemingly unique ability to stimulate the transcription of genes that are epigenetically poised for transcription and to amplify the transcription of actively transcribed genes. During lymphocyte activation, MYC is upregulated and stimulates a pro-proliferative program in part through the upregulation of a wide variety of metabolic effector genes that facilitate cell growth and cell cycle progression. MYC upregulation simultaneously sensitizes cells to apoptosis and activated lymphocytes and lymphoma cells have pro-survival attributes that allow MYC-driven proliferation to prevail. For example, the MAX-interacting protein MNT is upregulated in activated lymphocytes and was found to protect lymphocytes from MYC-dependent apoptosis. Here we review the activities of MYC, MNT and other MAX interacting proteins in the setting of T and B cell activation and oncogenesis. This article is part of a Special Issue entitled: Myc proteins in cell biology and pathology.
•We discuss the role of MYC in lymphocyte development, activation and lymphomagenesis.•We describe the MAX-interactome.•We highlight the role of MNT as a MYC antagonist and facilitator of MYC-dependent oncogenesis.