Mammalian Sug1 and c-Fos in the nuclear 26S proteasome.
In a search for regulatory proteins that interact with the leucine zipper motif of c-Fos in the yeast two-hybrid screen, we have identified a protein (FZA-B) that has extensive sequence similarity to SUG1 of Saccharomyces cerevisiae. Here we show that FZA-B can functionally substitute for SUG1 in yeast and that FZA-B interacts with Fos proteins in vitro through their leucine zippers. In rat liver and in HeLa cells, FZA-B is present in the 26S proteasome complex, as is c-Fos. Immobilized antibody raised against an FZA-B-specific peptide depleted peptidase activity, proteasomal proteins, FZA-B, and c-Fos from a 26S proteasome preparation. FZA-B is found predominantly in the nuclear fraction of COS cells expressing an FZA-B transgene and in the nuclear 26S proteasome of HeLa cells. We conclude that FZA-B is the mammalian homolog of SUG1 (mSug1) and that it is present in the nuclear 26S proteasome of cells. Our results suggest that mSug1 may be involved in the degradation of c-Fos and other transcription factors.
Wang
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Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Chevray
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Nathans
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D000074183:ATPases Associated with Diverse Cellular Activities; D000251:Adenosine Triphosphatases; D000595:Amino Acid Sequence; D000818:Animals; D002467:Cell Nucleus / Q000201:enzymology; D003546:Cysteine Endopeptidases / Q000737:chemistry*; D005656:Fungal Proteins / Q000737:chemistry*; D005816:Genetic Complementation Test; D016350:Leucine Zippers; D046911:Macromolecular Substances; D051379:Mice; D008969:Molecular Sequence Data; D009097:Multienzyme Complexes / Q000737:chemistry*; D009687:Nuclear Proteins / Q000737:chemistry* / Q000235:genetics*; D046988:Proteasome Endopeptidase Complex; D016760:Proto-Oncogene Proteins c-fos / Q000737:chemistry*; D051381:Rats; D012097:Repressor Proteins / Q000737:chemistry*; D012441:Saccharomyces cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid
D005656:Fungal Proteins; D046911:Macromolecular Substances; D009097:Multienzyme Complexes; D009687:Nuclear Proteins; D016760:Proto-Oncogene Proteins c-fos; C491455:Psmc5 protein, mouse; D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex; D000251:Adenosine Triphosphatases; C069670:RPT6 protein, S cerevisiae; D000074183:ATPases Associated with Diverse Cellular Activities