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A second degradation signal within the short‐lived transcription factor MATalpha2 (937.1)
Author(s) -
Hickey Christopher,
Hochstrasser Mark
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.937.1
Subject(s) - ubiquitin ligase , ubiquitin , transcription factor , proteasome , microbiology and biotechnology , genetics , biology , protein degradation , repressor , transcription (linguistics) , degradation (telecommunications) , chemistry , gene , computer science , telecommunications , linguistics , philosophy
The yeast transcriptional repressor MATalpha2 (alpha2) is a short‐lived protein known to be ubiquitylated by at least two distinct pathways, one involving the ubiquitin ligase (E3) Doa10 and the other operating with the E3 Slx5/Slx8. Simultaneous perturbation of both pathways leads to considerable stabilization of alpha2 (approximately 6‐fold); however, deletion of either pathway alone only leads to moderate stabilization of alpha2 (approximately 2‐fold). Although a degradation signal within alpha2, known as Deg1, is well established for Doa10‐dependent degradation, little is known about the determinants within alpha2 that direct its Doa10‐independent degradation. Here we report that alpha2 contains an additional degradation signal, termed Deg2, that is non‐overlapping with Deg1 and leads to ubiquitin‐dependent degradation when fused to normally long‐lived proteins. We also report numerous mutations within Deg2 that result in stabilization of alpha2, including several mutations in the homeodomain that impair the ability of alpha2 to interact with DNA. These data further our understanding of one of the best‐studied substrates of the ubiquitin‐proteasome system and highlight a previously encountered link between the ability of a transcription factor to function and its ubiquitin‐dependent degradation. Grant Funding Source : Supported by the U.S. National Institute of General Medical Sciences