Palindrome with spacer of one nucleotide is characteristic of the cis-acting unfolded protein response element in Saccharomyces cerevisiae.
When unfolded proteins are accumulated in the endoplasmic reticulum (ER), an intracellular signaling pathway termed the unfolded protein response (UPR) is activated to induce transcription of ER-localized molecular chaperones and folding enzymes in the nucleus. In Saccharomyces cerevisiae, at least six lumenal proteins including essential Kar2p and Pdi1p are known to be regulated by the UPR. We and others recently demonstrated that the basic-leucine zipper protein Hac1p/Ern4p functions as a trans-acting factor responsible for the UPR. Hac1p binds directly to the cis-acting unfolded protein response element (UPRE) responsible for Kar2p induction. Moreover, we showed that the KAR2 UPRE contains an E box-like palindrome separated by one nucleotide (CAGCGTG) that is essential for its function. We report here that the promoter regions of each of five target proteins (Kar2p, Pdi1p, Eug1p, Fkb2p, and Lhs1p) contain a single UPRE sequence that is necessary and sufficient for induction and that binds specifically to Hac1p in vitro. All of the five functional UPRE sequences identified contain a palindromic sequence that has, in four cases, a spacer of one C nucleotide. This unique characteristic of UPRE explains why only a specific set of proteins are induced in the UPR to cope with ER stress.
Mori
K
K
HSP Research Institute, Kyoto Research Park, Shimogyo-ku, Kyoto 600-8813, Japan. kazumori@hsp.co.jp
Ogawa
N
N
Kawahara
T
T
Yanagi
H
H
Yura
T
T
D001483:Base Sequence; D050976:Basic-Leucine Zipper Transcription Factors; D002467:Cell Nucleus / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000378:metabolism; D005656:Fungal Proteins / Q000096:biosynthesis* / Q000378:metabolism; D017930:Genes, Reporter; D006023:Glycoproteins / Q000096:biosynthesis*; D050956:HSP40 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins / Q000096:biosynthesis*; D006360:Heat-Shock Proteins / Q000096:biosynthesis; D018832:Molecular Chaperones / Q000096:biosynthesis / Q000378:metabolism*; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D019704:Protein Disulfide-Isomerases; D017510:Protein Folding; D012045:Regulatory Sequences, Nucleic Acid; D012097:Repressor Proteins / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins; D015398:Signal Transduction; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic; D001616:beta-Galactosidase / Q000096:biosynthesis
D050976:Basic-Leucine Zipper Transcription Factors; D005656:Fungal Proteins; D006023:Glycoproteins; C091341:HAC1 protein, S cerevisiae; D050956:HSP40 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins; D006360:Heat-Shock Proteins; C060153:KAR2 protein, yeast; D018832:Molecular Chaperones; C080576:PDI1 protein, S cerevisiae; D012097:Repressor Proteins; C067634:SCJ1 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; D001616:beta-Galactosidase; D019704:Protein Disulfide-Isomerases