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MAML1 mediates MEF2C degradation independent of ubiquitination (930.5)
Author(s) -
Zein Ivan,
White Brandon
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.930.5
Subject(s) - mef2c , microbiology and biotechnology , ubiquitin , proteasome , coactivator , chemistry , transcription factor , biology , biochemistry , gene
Myocyte Enhancer Factor 2C (MEF2C), a member of a family of transcription factors involved in muscle cell differentiation and proliferation, is known to interact with Mastermind‐like 1 (MAML1). MAML1 transcriptional coactivator was originally identified in the Notch pathway and is also involved in the beta‐catenin, p53, and MEF2C signaling pathways. MAML1 was previously shown to interact with MEF2C and is required for muscle development in the absence of Notch. Since MAML1 was shown to act as a coactivator of Notch while also to induce degradation of the Notch Intracellular Domain, we speculated whether or not MAML1 could also serve a similar function with MEF2C. Our results indicate that MEF2C is degraded in the presence of MAML1. However, this degradation is significantly reduced when using a MAML1 deletion mutant (75‐300). Furthermore, treatment with lactacystin, a proteasome inhibitor, did not inhibit MEF2C degradation while the use of lysosome inhibitors significantly attenuated MEF2C turnover. Our findings suggest that MEF2C degradation is mediated by MAML1 through a lysosomal degradation pathway, independent of the ubiquitin‐proteasomal pathway. Grant Funding Source : Supported by NSF‐RUI Grant#1052039 to JBW