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Genes 2017, 8(5), 134;

MB0 and MBI Are Independent and Distinct Transactivation Domains in MYC that Are Essential for Transformation

Department of Cell and Developmental Biology, Vanderbilt University, School of Medicine, 1121 21st Ave., Nashville, TN 37232, USA
These authors contributed equally to this work.
Author to whom correspondence should be addressed.
Academic Editor: Daitoku Sakamuro
Received: 10 February 2017 / Revised: 24 April 2017 / Accepted: 28 April 2017 / Published: 6 May 2017
(This article belongs to the Special Issue MYC Networks)
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MYC is a transcription factor that is essential for cellular proliferation and development. Deregulation or overexpression of MYC occurs in a variety of human cancers. Ectopic expression of MYC causes hyperproliferation and transformation of cells in culture and tumorigenesis in several transgenic mouse models. Deregulation of MYC can also induce apoptosis through activation of p53 and/or ARF tumor suppressors as a safeguard to prevent tumorigenesis. MYC binds to thousands of genomic sites and regulates hundreds of target genes in a context-dependent fashion to mediate these diverse biological roles. The N-terminal region of MYC contains several conserved domains or MYC Boxes (MB), which influence the different MYC transcriptional and biological activities to varying degrees. However, the specific domains that mediate the ability of MYC to activate transcription remain ill defined. In this report, we have identified a new conserved transactivation domain (TAD), MB0, which is essential for MYC transactivation and target gene induction. We demonstrate that MB0 and MBI represent two distinct and independent TADs within the N-terminal 62 amino acids of MYC. In addition, both MB0 and MBI are essential for MYC transformation of primary fibroblasts in cooperation with activated RAS, while MB0 is necessary for efficient MYC-induced p53-independent apoptosis. View Full-Text
Keywords: MYC; transcription; transactivation; transformation; apoptosis MYC; transcription; transactivation; transformation; apoptosis

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Zhang, Q.; West-Osterfield, K.; Spears, E.; Li, Z.; Panaccione, A.; Hann, S.R. MB0 and MBI Are Independent and Distinct Transactivation Domains in MYC that Are Essential for Transformation. Genes 2017, 8, 134.

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