The hydrophobic patch of ubiquitin is required to protect transactivator-promoter complexes from destabilization by the proteasomal ATPases.
Mono-ubiquitylation of a transactivator is known to promote transcriptional activation of certain transactivator proteins. For the Sacchromyces cerevisiae transactivator, GAL4, attachment of mono-ubiquitin prevents destabilization of the DNA-transactivator complex by the ATPases of the 26S proteasome. This inhibition of destabilization depends on the arrangement of ubiquitin; a chain of ubiquitin tetramers linked through lysine 48 did not display the same protective effect as mono-ubiquitin. This led to an investigation into the properties of ubiquitin that may be responsible for this difference in activity between the different forms. We demonstrate the ubiquitin tetramers linked through lysine 63 do protect from proteasomal-mediated destabilization. In addition, we show that the mutating the isoleucine residue at position 44 interferes with proteasomal interaction in vitro and will abolish the protective activity in vivo. Together, these data implicate the hydrophobic patch of ubiquitin as required to protect transactivators from destabilization by the proteasomal ATPases.
Archer
Chase T
CT
Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390-9185, USA.
Kodadek
Thomas
T
D000251:Adenosine Triphosphatases / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D057927:Hydrophobic and Hydrophilic Interactions; D007532:Isoleucine / Q000235:genetics; D009154:Mutation; D011401:Promoter Regions, Genetic; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D025801:Ubiquitin / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism
D004268:DNA-Binding Proteins; C052130:GAL4 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D025801:Ubiquitin; D007532:Isoleucine; D046988:Proteasome Endopeptidase Complex; D000251:Adenosine Triphosphatases; C084493:RPT1 protein, S cerevisiae