The hydrophobic patch of ubiquitin is required to protect transactivator–promoter complexes from destabilization by the proteasomal ATPases

Article (PDF Available)inNucleic Acids Research 38(3):789-96 · November 2009with10 Reads
DOI: 10.1093/nar/gkp1066 · Source: PubMed
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.

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Available from: Thomas Kodadek, Apr 13, 2016
    • "Subsequently, however, it was argued that Gal4 remains stably bound to the enhancer under inducing conditions, suggesting that proteolytic turnover of Gal4 might not be required for its function212223 . Previously, it had been shown that monoubiquitination protected Gal4 from the promoter-stripping activity of proteasomal ATPases242526, suggesting a role for ubiquitin in transcriptional activation other than protein degradation. Recently , it has been reported that the proteolytic stability of Mediator subunits is inversely correlated with their ability to activate transcription when fused to a DNA-binding domain [27]. "
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