Redundancy and variation in the ubiquitin-mediated proteolytic targeting of a transcription factor.

摘要: As central components of the intricate networks eukaryotic gene regulation, transcription factors are frequent targets ubiquitin-dependent proteolysis. A well-known example is budding yeast MATα2 (α2) transcriptional repressor, which functions as a master regulator cell-type determination. Degradation α2 by ubiquitin-proteasome system necessary for phenotypic switch from one cell type to another. surprisingly complex set ubiquitin-protein conjugation mechanisms involved. One pathway utilizes an integral-membrane ubiquitin ligase (E3) that also in endoplasmic reticulum-associated degradation (ERAD). Recently, we showed second ubiquitylation uses heterodimeric E3 that, while able bind ubiquitin-like protein SUMO, directly recognizes non-sumoylated α2. Other now known be ubiquitylated multiple mechanisms; many dozen E3s have been implicated human p53 tumor suppressor, example. We discuss general issues redundancy and mechanistic variation modification ubiquitin.