Biological Activity
C-myc oncogene has high proliferative capacity. Overexpression of this gene is associated with Burkitt lymphoma. C-myc oncogene is implicated in various malignant tumors, such as, leukemia, lymphoma and human solid tumor.', 'The universal deregulation of c-Myc gene expression in tumor cells suggests th at this oncogene represents an attractive target for cancer therapeutic purposes. The c-Myc promoter integrates diverse mitogenic signaling cascades, which are constitutively activated in tumor cells, and translates them into expression of the c-Myc transcription factor, which promotes cell proliferation, growth, differentiation, and apoptosis by regulating the expression of numerous target genes. The structural and biochemical features of the MYC family (MYC, N-MYC, and L-MYC) mark them as direct regulators of gene expression. As basic helix-loop-helix leucine zipper proteins (bHLH-ZIP), the MYCs acquire the capacity to bind the DNA sequence CACGTG (E-box) when dimerized with MAX (another bHLH-ZIP, 4,5). A head-to-tail pair of MYC-MAX dimers may, in turn, form a heterotetramer capable of bridging distant E-boxes. Among the broadly distributed positive enforcers of MYC action th at are often recruited to target genes are chromatin remodeling (SWI/SNF relatives) and modifying complexes (TRAPP/GCN5 and relatives); these complexes mobilize nucleosomes and acetylate histones and/or other targets to activate gene expression. MYC binds TBP along an auxiliary pathway to control gene expression. MAD and MNT generally oppose MYC action by enlisting histone deacetylase complexes. Besides acting at the level of chromatin, MYC may also operate at later stages of the transcription cycle, after pre-initiation complex formation. In addition to using generic chromatin complexes to up- or down-regulate transcription, the MYC network also conscripts individual factors to modify expression locally on an ad hoc basis. For example, YY1, AP2, MIZ1, SP1, BRCA1, and other proteins interact directly with MYC, and so may directly modify the output of the MYC network.
