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Mastermind‐like 1 is ubiquitinated: functional consequences for notch signaling
Author(s) -
White Brandon,
Farshbaf Mozhgan,
Lindberg Mikael J.,
Behmner Stefanie,
Wallberg Annika E
Publication year - 2012
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.26.1_supplement.734.9
Subject(s) - notch signaling pathway , ubiquitin , biology , microbiology and biotechnology , transcription factor , signal transduction , gene , genetics
The Mastermind‐like (MAML) proteins are transcriptional coactivators for Notch signaling, an evolutionarily conserved pathway that plays several key roles in development and in human disease. The MAML family contains MAML1, MAML2, and MAML3. We have identified MAML1 to be ubiquitinated. Deletion analysis shows that ubiquitination occurs in the first 301 amino acids of MAML1. MAML1 half‐life was calculated to be ~3 hours which is similar to half‐life reported for Notch. Overexpression of p300 stimulates ubiquitination of MAML1, but is independent of the p300 acetyl‐transferase activity. Finally, overexpression of Notch with MAML1 decreases ubiquitination. These results suggest that MAML1 may be turned‐over to maintain low protein levels in the absence of Notch. Upon Notch cleavage and translocation to the nucleus, MAML1 becomes more stable to help form the ternary complex for transcriptional activation of target genes. This research was supported by an NSF‐RUI Grant#1052039 to JBW, and grants from the Swedish Research Council, the Swedish Cancer Society, and the Swedish Children's Cancer Foundation to A.E.W. M.J.L. was supported by a fellowship from the Swedish Children's Cancer Foundation and a grant from Alex and Eva Wallstrom foundation.