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001-es BibID:	BIBFORM122712
035-os BibID:	(Scopus)85194736410 (WoS)001234571700001
Első szerző:	Martí-Andrés, Pablo
Cím:	TRP14 is the rate-limiting enzyme for intracellular cystine reduction and regulates proteome cysteinylation / Pablo Martí-Andrés, Isabela Finamor, Isabel Torres-Cuevas, Salvador Pérez, Sergio Rius-Pérez, Hildegard Colino-Lage, David Guerrero-Gómez, Esperanza Morato, Anabel Marina, Patrycja Michalska, Rafael León, Qing Cheng, Eszter Petra Jurányi, Klaudia Borbényi-Galambos, Iván Millán, Péter Nagy, Antonio Miranda-Vizuete, Edward E. Schmidt, Antonio Martínez-Ruiz, Elias S. J. Arnér, Juan Sastre
Dátum:	2024
ISSN:	1460-2075
Megjegyzések:	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 knockout 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 knockout mice were, surprisingly, protected in an acute pancreatitis model, concomitant with activation of Nrf2-driven antioxidant pathways and upregulation of transsulfuration. We conclude that TRP14 is the evolutionarily conserved enzyme principally responsible for intracellular cystine reduction in C. elegans, mice, and humans. ? The Author(s) 2024.
Tárgyszavak:	Orvostudományok Klinikai orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban folyóiratcikk Acute Pancreatitis Cysteine Homeostasis Protein Cysteinylation Proteotoxic Stress Transsulfuration
Megjelenés:	The EMBO Journal. - 43 : 13 (2024), p. 2789-2812. -
További szerzők:	Finamor, Isabela Torres-Cuevas, Isabel Pérez, Salvador Rius-Pérez, Sergio Colino-Lage, Hildegard Guerrero-Gómez, David Morato, Esperanza Marina, Anabel Michalska, Patrycja León, Rafael Cheng, Qing Jurányi Eszter Petra Galambos Klaudia (1995-) (biológus) Millán Iván Nagy Péter (1976-) (vegyész) Miranda-Vizuete, Antonio Schmidt, Edward E. Martínez-Ruiz, Antonio Arner, Elias S. J. Sastre, Juan
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