biostudies-literatureUnknown128(9)Mathuranyanon RAccumulation of unfolded proteins in the endoplasmic reticulum (ER) accompanies ER stress and causes the type-I transmembrane protein Ire1 (also known as ERN1) to trigger the unfolded protein response (UPR). When dimerized, the core stress-sensing region (CSSR) of Ire1 directly captures unfolded proteins and forms a high-order oligomer, leading to clustering and activation of Ire1. The CSSR is N-terminally flanked by an intrinsically disordered subdomain, which we previously named Subregion I, in Saccharomyces cerevisiae Ire1. In this study, we describe tight repression of Ire1 activity by Subregion I under conditions of no or weak stress. Weak hyperactivation of an Ire1 mutant lacking Subregion I slightly retarded growth of yeast cells cultured under unstressed conditions. Fungal Ire1 ortJournal of cell science1762-72https://www.ebi.ac.uk/biostudies/studies/S-EPMC4432228biostudies-literatureTight regulation of the unfolded protein sensor Ire1 by its intramolecularly antagonizing subdomain.PMC4432228Tsukamoto TTakeuchi AMathuranyanon RIshiwata-Kimata YKohno KKimata YTsuchiya YfalseTight regulation of the unfolded protein sensor Ire1 by its intramolecularly antagonizing subdomain.Accumulation of unfolded proteins in the endoplasmic reticulum (ER) accompanies ER stress and causes the type-I transmembrane protein Ire1 (also known as ERN1) to trigger the unfolded protein response (UPR). When dimerized, the core stress-sensing region (CSSR) of Ire1 directly captures unfolded proteins and forms a high-order oligomer, leading to clustering and activation of Ire1. The CSSR is N-terminally flanked by an intrinsically disordered subdomain, which we previously named Subregion I, in Saccharomyces cerevisiae Ire1. In this study, we describe tight repression of Ire1 activity by Subregion I under conditions of no or weak stress. Weak hyperactivation of an Ire1 mutant lacking Subregion I slightly retarded growth of yeast cells cultured under unstressed conditions. Fungal Ire1 ort2015-01-01T00:00:00Z2015 May2025-05-29T19:12:50.044Z2019-03-27T01:51:38ZS-EPMC44322282577010110.1242/jcs.164111