TRP14 is the rate-limiting enzyme for intracellular cystine reduction and regulates proteome cysteinylation

ABSTRACT: It has remained unknown how cells reduce cystine taken up from the extracellular space, which is a required step for further utilization of cysteine in key processes such as protein or glutathione synthesis. Here we show that the thioredoxin-related protein of 14 kDa (TRP14, encoded by TXNDC17) is the rate-limiting enzyme for intracellular cystine reduction. When TRP14 is genetically knocked out, cysteine synthesis through the transsulfuration pathway becomes the major source of cysteine in human cells, and knock-out of both pathways becomes lethal in C. elegans subjected to proteotoxic stress. TRP14 can also reduce cysteinyl moieties on proteins, rescuing their activities as here shown with cysteinylated peroxiredoxin 2. Txndc17 knock-out mice were, surprisingly, protected in an acute pan

SUBMITTER: Dr. Pablo Martí-Andrés 

PROVIDER: S-SCDT-10_1038-S44318-024-00117-1 | biostudies-other |

REPOSITORIES: biostudies-other