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 (E R), an intracellular signaling pathway termed the unfolded protein res ponse (UPR) is activated to induce transcription of ER-localized molec ular chaperones and folding enzymes in the nucleus. In Saccharomyces c erevisiae, at least six lumenal proteins including essential Kar2p and Pdi1p are known to be regulated by the UPR. We and others recently de monstrated that the basic-leucine zipper protein Hac1p/Ern4p functions as a trans-acting factor responsible for the UPR. Hac1p binds directl y to the cis-acting unfolded protein response element (UPRE) responsib le for Kar2p induction. Moreover, we showed that the KAR2 UPRE contain s an E box-like palindrome separated by one nucleotide (CAGCGTG) that is essential for its function. We report here that the promoter region s of each of five target proteins (Kar2p, Pdi1p, Eug1p, Fkb2p, and Lhs 1p) contain a single UPRE sequence that is necessary and sufficient fo r induction and that binds specifically to Hac1p in vitro. All of the five functional UPRE sequences identified contain a palindromic sequen ce that has, in four cases, a spacer of one C nucleotide. This unique characteristic of UPRE explains why only a specific set of proteins ar e induced in the UPR to cope with ER stress.