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Publication : The MYC-WDR5 Nexus and Cancer.

First Author  Thomas LR Year  2015
Journal  Cancer Res Volume  75
Issue  19 Pages  4012-5
PubMed ID  26383167 Mgi Jnum  J:225948
Mgi Id  MGI:5695378 Doi  10.1158/0008-5472.CAN-15-1216
Citation  Thomas LR, et al. (2015) The MYC-WDR5 Nexus and Cancer. Cancer Res 75(19):4012-5
abstractText  The MYC oncogenes encode a family of transcription factors that feature prominently in cancer. MYC proteins are overexpressed or deregulated in a majority of malignancies and drive tumorigenesis by inducing widespread transcriptional reprogramming that promotes cell proliferation, metabolism, and genomic instability. The ability of MYC to regulate transcription depends on its dimerization with MAX, which creates a DNA-binding domain that recognizes specific sequences in the regulatory elements of MYC target genes. Recently, we discovered that recognition of target genes by MYC also depends on its interaction with WDR5, a WD40-repeat protein that exists as part of several chromatin-regulatory complexes. Here, we discuss how interaction of MYC with WDR5 could create an avidity-based chromatin recognition mechanism that allows MYC to select its target genes in response to both genetic and epigenetic determinants. We rationalize how the MYC-WDR5 interaction provides plasticity in target gene selection by MYC and speculate on the biochemical and genomic contexts in which this interaction occurs. Finally, we discuss how properties of the MYC-WDR5 interface make it an attractive point for discovery of small-molecule inhibitors of MYC function in cancer cells. Cancer Res; 75(19); 4012-5. (c)2015 AACR.
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