High impact information on RPT6

• The fusion proteins glutathione S-transferase (GST)-Rad23 and Rad4-haemagglutinin (HA), and the proteasome subunits Cim3 and Cim5, cofractionate through consecutive chromatography steps [1].
• Mutations in SUG1 were isolated as suppressors of a mutation in the transcriptional activation domain of GAL4 [2].
• Our observations account for the reduced ubiquitin-dependent proteolysis in sug1 mutants and suggest that the effects of sug1 mutations on transcription are indirect results of defective proteolysis [2].
• Sug1 is a member of a large, highly conserved family of ATPases, implying a role for ATP hydrolysis in the activation of transcription [3].
• Here, we demonstrate that proteasomal ATPases Rpt4 and Rpt6 function to connect these two histone modifications [4].

Biological context of RPT6

• First, yeast strains carrying alleles of SUG1 and SUG2, encoding 19S components, exhibit phenotypes indicative of elongation defects [5].
• Sug1 modulates yeast transcription activation by Cdc68 [6].
• We report here the molecular characterization of mutations in one suppressor gene, the previously identified SUG1 gene [6].
• We show that recruitment of proteasome subunits to chromatin depends on H2B ubiquitylation and that mutations in Rpt4 and Rpt6 disrupt H3 methylation at K4 and K79 but leave H2B ubiquitylation intact [4].
• In Saccharomyces cerevisiae, the SCL-1 mutation is a dominant suppressor of the cycloheximide-resistant, temperature-sensitive (ts) lethal mutation, crl3 [McCusker and Haber, Genetics 119 (1988a) 303-315] [7].

Associations of RPT6 with chemical compounds

• The substituted 6-chloro-2-pyrones are slowly hydrolyzed in the presence of CRL1 and are pseudosubstrates of CRL3, but are simple reversible inhibitors of pancreatic cholesterol esterase[8]
• Inhibition of CRL3 by substituted 6-chloro-2-pyrones was competitive with binding of the substrate p-nitrophenyl butyrate [8].
• Molecular modeling studies suggest that the orientation of binding of these inhibitors at the active site of CRL3 can vary but that the pyrone ring consistently occupies a position close to the active site serine [8].

Physical interactions of RPT6

• Sug1p has previously been shown to bind the Gal4 AD in vitro [9].

Regulatory relationships of RPT6

• Surprisingly, the overall structure of the PRS2 gene was found to be identical to that of the suppressor scl1+ gene restoring the SCL1-1 mutation that suppresses crl3 cycloheximide-resistant, temperature-sensitive lethality [10].

Other interactions of RPT6

• The 201-residue amino-terminal region of UFD4 is essential for its binding to RPT4 and RPT6 [11].
• Sug1 and Sug2 are two of six ATPases in the 19S regulatory particle of the 26S proteasome [12].
• Furthermore, chromatin immunoprecipitation analysis revealed the recruitment of Sug1, Sug2 and Cim5 (another of the ATPases), but not 20S proteasome core proteins, to the promoters of these genes [12].
• SUG2 and SUG1, another 19 S component, were originally discovered as a mutation able to suppress the phenotype of a Gal4 truncation mutant (Gal4(D)p) lacking much of its AD [9].
• In contrast, proteasome-defective rpt6/cim3 mutants accumulate polyubiquitinated Gpa1, and in this case the protein exhibits cytoplasmic localization [13].

Analytical, diagnostic and therapeutic context of RPT6

• Sug1 co-purifies with the proteasome in both conventional and nickel-chelate affinity chromatography [2].

References