title: Redundancy and variation in the ubiquitin-mediated proteolytic targeting of a transcription factor.
abstract: As central components of the intricate networks of eukaryotic gene regulation, transcription factors are frequent targets of ubiquitin-dependent proteolysis. A well-known example is the budding yeast MATα2 (α2) transcriptional repressor, which functions as a master regulator of cell-type determination. Degradation of α2 by the ubiquitin-proteasome system is necessary for a phenotypic switch from one cell type to another. A surprisingly complex set of ubiquitin-protein conjugation mechanisms are involved. One pathway utilizes an integral-membrane ubiquitin ligase (E3) that also functions in endoplasmic reticulum-associated degradation (ERAD). Recently, we showed that a second α2 ubiquitylation pathway uses a heterodimeric E3 that, while able to bind the ubiquitin-like protein SUMO, directly recognizes non-sumoylated α2. Other transcription factors are now also known to be ubiquitylated by multiple mechanisms; as many as a dozen E3s have been implicated in degradation of the human p53 tumor suppressor, for example. We discuss general issues of redundancy and mechanistic variation in protein modification by ubiquitin.
authors.affiliation: Department of Molecular Biophysics & Biochemistry, Yale University, New Haven, CT, USA.
authors.forename: Eric M
authors.initials: EM
authors.lastname: Rubenstein
authors.forename: Mark
authors.initials: M
authors.lastname: Hochstrasser
mesh_terms: D004721:Endoplasmic Reticulum / Q000378:metabolism; D006801:Humans; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D012097:Repressor Proteins / Q000378:metabolism*; D025842:SUMO-1 Protein / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D025801:Ubiquitin / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism; D054875:Ubiquitination
chemical_list: C062928:MATA2 protein, S cerevisiae; D012097:Repressor Proteins; D025842:SUMO-1 Protein; D029701:Saccharomyces cerevisiae Proteins; D016159:Tumor Suppressor Protein p53; D025801:Ubiquitin; D044767:Ubiquitin-Protein Ligases; D046988:Proteasome Endopeptidase Complex