title: Modulation of cellular disulfide-bond formation and the ER redox environment by feedback regulation of Ero1.
abstract: Introduction of disulfide bonds into proteins entering the secretory pathway is catalyzed by Ero1p, which generates disulfide bonds de novo, and Pdi1p, which transfers disulfides to substrate proteins. A sufficiently oxidizing environment must be maintained in the endoplasmic reticulum (ER) to allow for disulfide formation, but a pool of reduced thiols is needed for isomerization of incorrectly paired disulfides. We have found that hyperoxidation of the ER is prevented by attenuation of Ero1p activity through noncatalytic cysteine pairs. Deregulated Ero1p mutants lacking certain cysteines show increased enzyme activity, a decreased lag phase in kinetic assays, and growth defects in vivo. We hypothesize that noncatalytic cysteine pairs in Ero1p sense the level of potential substrates in the ER and correspondingly modulate Ero1p activity as part of a homeostatic regulatory system governing the thiol-disulfide balance in the ER.
authors: Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
authors: Carolyn S
authors: CS
authors: Sevier
authors: Hongjing
authors: H
authors: Qu
authors: Nimrod
authors: N
authors: Heldman
authors: Einav
authors: E
authors: Gross
authors: Deborah
authors: D
authors: Fass
authors: Chris A
authors: CA
authors: Kaiser
mesh_terms: D003553:Cystine / Q000378:metabolism; D004220:Disulfides / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000737:chemistry / Q000378:metabolism*; D025461:Feedback, Physiological; D006023:Glycoproteins / Q000378:metabolism*; D010084:Oxidation-Reduction; D050862:Oxidoreductases Acting on Sulfur Group Donors; D012441:Saccharomyces cerevisiae / Q000254:growth & development / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*
chemical_list: D004220:Disulfides; D006023:Glycoproteins; D029701:Saccharomyces cerevisiae Proteins; D003553:Cystine; D050862:Oxidoreductases Acting on Sulfur Group Donors; C113186:ERO1 protein, S cerevisiae