A novel mechanism for regulating activity of a transcription factor that controls the unfolded protein response.
Cells respond to an accumulation of unfolded proteins in the endoplasmic reticulum (ER) by increasing transcription of genes encoding ER-resident proteins. The information is transmitted from the ER lumen to the nucleus by an intracellular signaling pathway, the unfolded protein response (UPR). We have identified a basic-leucine zipper transcription factor, Hac1p, that is required for the UPR and binds to the UPR element in the promoter of UPR-regulated genes. Surprisingly, Hac1p is found in UPR-activated cells only, and its level is controlled by regulated splicing of its mRNA. Splicing replaces the C-terminal tail of Hac1p with a different peptide that renders Hac1p more resistant to an otherwise extremely rapid ubiquitin-dependent degradation. We propose that the complex regulation of Hac1p expression serves to provide multiple levels at which the UPR can be controlled.
Cox
J S
JS
Department of Biochemistry and Biophysics, University of California, School of Medicine, San Francisco 94143-0448, USA.
Walter
P
P
D000595:Amino Acid Sequence; D050976:Basic-Leucine Zipper Transcription Factors; D004271:DNA, Fungal / Q000235:genetics; D010450:Endopeptidases / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000502:physiology*; D005656:Fungal Proteins / Q000235:genetics* / Q000502:physiology; D015966:Gene Expression Regulation, Fungal; D008562:Membrane Glycoproteins / Q000235:genetics / Q000502:physiology; D018832:Molecular Chaperones / Q000096:biosynthesis* / Q000235:genetics; D008969:Molecular Sequence Data; D010641:Phenotype; D017510:Protein Folding; D017346:Protein Serine-Threonine Kinases; D012326:RNA Splicing; D012331:RNA, Fungal / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D012045:Regulatory Sequences, Nucleic Acid; D012097:Repressor Proteins / Q000235:genetics* / Q000502:physiology; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000502:physiology; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; D014158:Transcription, Genetic; D014452:Ubiquitins / Q000378:metabolism
D050976:Basic-Leucine Zipper Transcription Factors; D004271:DNA, Fungal; D005656:Fungal Proteins; C091341:HAC1 protein, S cerevisiae; D008562:Membrane Glycoproteins; D018832:Molecular Chaperones; D012331:RNA, Fungal; D012333:RNA, Messenger; D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; D014452:Ubiquitins; C082863:IRE1 protein, S cerevisiae; D017346:Protein Serine-Threonine Kinases; D010450:Endopeptidases