Characterization of Ire1 in the yeast Yarrowia lipolytica reveals an important role for the Sls1 nucleotide exchange factor in unfolded protein response regulation.
Following endoplasmic reticulum (ER) stress, eukaryotic cells trigger a conserved signal transduction pathway called the unfolded protein response (UPR) that regulates the ER's capacity to perform protein folding according to cellular demand. In Saccharomyces cerevisiae, the UPR is initiated by Ire1, a type I transmembrane serine/threonine kinase/endoribonuclease, that senses unfolded protein levels within the ER in collaboration with the ER Hsp70-family member, BiP/Kar2. Here, we report on the characterization of the Yarrowia lipolytica Ire1 ortholog. Our results show that Sls1, a nucleotide exchange factor for BiP, has important functions in regulating ER stress and the interaction of BiP and Ire1. They suggest that Sls1 regulates this interaction, by stimulating the conversion of BiP from the ADP-bound to the ATP-bound state, which favors its interaction with Ire1. Moreover, we identified known and new partners for Ire1 using the Tandem Affinity Purification (TAP) approach.
Babour
Anna
A
University of California, San Diego, NSB 5315 9500 Gilman Drive, La Jolla, CA 92093, USA. ababour@biomail.ucsd.edu
Kabani
Mehdi
M
Boisramé
Anita
A
Beckerich
Jean-Marie
JM
D000595:Amino Acid Sequence; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D004722:Endoribonucleases / Q000378:metabolism*; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism*; D015966:Gene Expression Regulation, Fungal; D005800:Genes, Fungal; D008969:Molecular Sequence Data; D009711:Nucleotides / Q000235:genetics / Q000378:metabolism; D017510:Protein Folding; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D016415:Sequence Alignment; D025062:Yarrowia / Q000201:enzymology / Q000235:genetics / Q000378:metabolism*
D002352:Carrier Proteins; D005656:Fungal Proteins; D009711:Nucleotides; D017346:Protein Serine-Threonine Kinases; D004722:Endoribonucleases