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Mastermind-like transcriptional co-activators: emerging roles in regulating cross talk among multiple signaling pathways

Oncogene volume 27, pages 5138–5147 (2008)Cite this article

Abstract

A family of Mastermind-like (MAML) genes encodes critical transcriptional co-activators for Notch signaling, an evolutionarily conserved pathway with numerous roles in both development and human diseases. Notch receptors are cleaved upon ligand engagement and the intracellular domain of Notch shuttles to the nucleus. MAMLs form a functional DNA-binding complex with the cleaved Notch receptor and the transcription factor CSL, thereby regulating transcriptional events that are specific to the Notch pathway. Here, we review recent studies that have utilized molecular, cellular and physiological model system strategies to reveal the pivotal roles of the MAML proteins in Notch signaling. Unexpectedly, however, emerging evidence implicate MAML proteins as exciting key transcriptional co-activators in other signal transduction pathways including: muscle differentiation and myopathies (MEF2C), tumor suppressor pathway (p53) and colon carcinoma survival (β-catenin). Thus, the MAML family appears to function in transcriptional co-activation in a multitude of cellular processes. It is hypothesized that MAML proteins mediate cross-talk among the various signaling pathways and the diverse activities of the MAML proteins converge to impact normal biological processes and human diseases, including cancers.

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Acknowledgements

This work was supported in part by NIH (R01 CA097148) and Muscular Dystrophy Association (MDA).

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Authors and Affiliations

  1. Ventana Medical Systems Inc., Tucson, AZ, USA

    A S McElhinny

  2. Interdisciplinary Center for Biotechnology Research, University of Florida, Gainesville, FL, USA

    J-L Li

  3. Department of Molecular Genetics and Microbiology, Shands Cancer Center, University of Florida, Gainesville, FL, USA

    L Wu

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  1. A S McElhinny
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Correspondence to L Wu.

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McElhinny, A., Li, JL. & Wu, L. Mastermind-like transcriptional co-activators: emerging roles in regulating cross talk among multiple signaling pathways. Oncogene 27, 5138–5147 (2008). https://doi.org/10.1038/onc.2008.228

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