title: Ubiquitin signals proteolysis-independent stripping of transcription factors.
abstract: Ubiquitination of transcription activators has been reported to regulate transcription via both proteolytic and nonproteolytic routes, yet the function of the ubiquitin (Ub) signal in the nonproteolytic process is poorly understood. By use of the heterologous transcription activator LexA-VP16 in Saccharomyces cerevisiae, we show that monoubiquitin fusion of the activator prevents stable interactions between the activator and DNA, leading to transcription inhibition without activator degradation. We identify the AAA(+) ATPase Cdc48 and its cofactors as the Ub receptor responsible for extracting the monoubiquitinated activator from DNA. Our results suggest that deubiquitination of the activator is critical for transcription activation. These findings with LexA-VP16 extend in both yeast and mammalian cells to native transcription activators Met4 and R-Smads, respectively, that are known to be oligo-ubiquitinated. The results illustrate a role for Ub and Cdc48 in transcriptional regulation and gene expression that is independent of proteolysis.
authors.affiliation: Department of Biochemistry and Molecular Biology, Colorado State University, Fort Collins, CO 80523, USA.
authors.forename: Ada
authors.initials: A
authors.lastname: Ndoja
authors.affiliation: Department of Biochemistry and Molecular Biology, Colorado State University, Fort Collins, CO 80523, USA.
authors.forename: Robert E
authors.initials: RE
authors.lastname: Cohen
authors.affiliation: Department of Biochemistry and Molecular Biology, Colorado State University, Fort Collins, CO 80523, USA. Electronic address: tingting.yao@colostate.edu.
authors.forename: Tingting
authors.initials: T
authors.lastname: Yao
mesh_terms: D000251:Adenosine Triphosphatases / Q000235:genetics* / Q000378:metabolism; D050976:Basic-Leucine Zipper Transcription Factors / Q000235:genetics* / Q000378:metabolism; D001665:Binding Sites; D018797:Cell Cycle Proteins / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D004247:DNA / Q000235:genetics / Q000378:metabolism; D006801:Humans; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D011485:Protein Binding; D059748:Proteolysis; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction; D051896:Smad Proteins, Receptor-Regulated / Q000235:genetics* / Q000378:metabolism; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D025801:Ubiquitin / Q000235:genetics* / Q000378:metabolism; D054875:Ubiquitination; D000074405:Valosin Containing Protein
chemical_list: D050976:Basic-Leucine Zipper Transcription Factors; D018797:Cell Cycle Proteins; C073675:MET4 protein, S cerevisiae; D009687:Nuclear Proteins; D029701:Saccharomyces cerevisiae Proteins; D051896:Smad Proteins, Receptor-Regulated; D025801:Ubiquitin; C094680:nuclear protein import factor p97; D004247:DNA; D000251:Adenosine Triphosphatases; C000614177:CDC48 protein, S cerevisiae; D000074405:Valosin Containing Protein