SUMMARY PARAGRAPH for HAC1
HAC1 encodes a transcription factor of the basic leucine zipper (bZIP) family that is involved in the unfolded protein response (13, 1, 5). Heat stress, drug treatment, mutations in secretory proteins, or overexpression of wild type secretory proteins can cause unfolded proteins to accumulate in the endoplasmic reticulum (ER), triggering the unfolded protein response (UPR). Increased transcription of genes encoding soluble ER resident proteins, including chaperones, is a key feature of the UPR (see reference 8 for a review of the UPR).
HAC1 is not essential under normal growth conditions, but is essential under conditions that trigger the UPR (13, 8). Hac1p binds to a DNA sequence called the UPR element (UPRE), probably as a homodimer (14, 1, 9, 8). Hac1p also regulates expression of genes encoding proteins involved in phospholipid biosynthesis (8). The abundance of Hac1p is regulated by splicing of the HAC1 mRNA, which proceeds by an unconventional mechanism (6, 10, 8). The protein kinase involved in UPR signaling, Ire1p, has an endoribonuclease activity that cleaves the HAC1 mRNA to remove an intron located near the 3' end of the transcript (7, 11, 8). The exons are ligated by Trl1p, the RNA ligase involved in tRNA processing (15, 7). The spliced HAC1 mRNA is translated much more efficiently than the unspliced transcript (6, 10, 8).
Transcription of UPR target genes also involves the SAGA histone acetyltransferase complex (comprising Gcn5p, Hfi1p, Ada2p, Ngg1p, Spt20p, Spt3p, and Spt7p); Gcn5p interacts physically with Ire1p (16, 3, 8). Spt20p interacts with both Hac1p and Ire1p, and is required for HAC1 mRNA splicing in vivo (3).
The UPR is conserved in mammals; although no mammalian homolog of Hac1p has been identified, mammalian cell extracts can splice the yeast HAC1 mRNA (8).
Last updated: 2000-04-10