Redundancy and variation in the ubiquitin-mediated proteolytic targeting of a transcription factor.
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.
Rubenstein
Eric M
EM
Department of Molecular Biophysics & Biochemistry, Yale University, New Haven, CT, USA.
Hochstrasser
Mark
M
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
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