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

Oncogene. 2008 Sep 1;27(38):5138-47. doi: 10.1038/onc.2008.228.


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 (beta-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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adenocarcinoma / physiopathology
  • Animals
  • Cell Communication / physiology
  • Cell Differentiation / physiology
  • Colonic Neoplasms / physiopathology
  • DNA-Binding Proteins / chemistry
  • DNA-Binding Proteins / physiology*
  • Humans
  • MADS Domain Proteins / deficiency
  • MADS Domain Proteins / physiology
  • MEF2 Transcription Factors
  • Mice
  • Mice, Knockout
  • Multiprotein Complexes
  • Muscular Diseases / genetics
  • Muscular Diseases / pathology
  • Myogenic Regulatory Factors / physiology
  • Organ Specificity
  • Protein Interaction Mapping
  • Receptors, Notch / chemistry
  • Receptors, Notch / physiology*
  • Signal Transduction / physiology*
  • Trans-Activators / chemistry
  • Trans-Activators / physiology*
  • Transcription Factors
  • Transcriptional Activation / physiology*
  • Tumor Suppressor Protein p53 / physiology
  • Tumor Suppressor Proteins / physiology
  • beta Catenin / physiology


  • DNA-Binding Proteins
  • MADS Domain Proteins
  • MAML1 protein, human
  • MEF2 Transcription Factors
  • MEF2C protein, human
  • Multiprotein Complexes
  • Myogenic Regulatory Factors
  • Receptors, Notch
  • Trans-Activators
  • Transcription Factors
  • Tumor Suppressor Protein p53
  • Tumor Suppressor Proteins
  • beta Catenin