S-nitrosylation-triggered unfolded protein response maintains hematopoietic progenitors in Drosophila.

Autor:	Cho B; Department of Life Science, College of Natural Science, Hanyang University, Seoul 04763, Republic of Korea; Research Institute for Natural Science, Hanyang University, Seoul 04763, Republic of Korea., Shin M; Department of Life Science, College of Natural Science, Hanyang University, Seoul 04763, Republic of Korea., Chang E; Department of Life Science, College of Natural Science, Hanyang University, Seoul 04763, Republic of Korea., Son S; Department of Life Science, College of Natural Science, Hanyang University, Seoul 04763, Republic of Korea., Shin I; Department of Life Science, College of Natural Science, Hanyang University, Seoul 04763, Republic of Korea; Research Institute for Natural Science, Hanyang University, Seoul 04763, Republic of Korea; Research Institute for Convergence of Basic Science, Hanyang University, Seoul 04763, Republic of Korea., Shim J; Department of Life Science, College of Natural Science, Hanyang University, Seoul 04763, Republic of Korea; Research Institute for Natural Science, Hanyang University, Seoul 04763, Republic of Korea; Research Institute for Convergence of Basic Science, Hanyang University, Seoul 04763, Republic of Korea; Hanyang Institute of Bioscience and Biotechnology, Hanyang University, Seoul 04763, Republic of Korea. Electronic address: jshim@hanyang.ac.kr.
Jazyk:	angličtina
Zdroj:	Developmental cell [Dev Cell] 2024 Apr 22; Vol. 59 (8), pp. 1075-1090.e6. Date of Electronic Publication: 2024 Mar 22.
DOI:	10.1016/j.devcel.2024.02.013
Abstrakt:	The Drosophila lymph gland houses blood progenitors that give rise to myeloid-like blood cells. Initially, blood progenitors proliferate, but later, they become quiescent to maintain multipotency before differentiation. Despite the identification of various factors involved in multipotency maintenance, the cellular mechanism controlling blood progenitor quiescence remains elusive. Here, we identify the expression of nitric oxide synthase in blood progenitors, generating nitric oxide for post-translational S-nitrosylation of protein cysteine residues. S-nitrosylation activates the Ire1-Xbp1-mediated unfolded protein response, leading to G2 cell-cycle arrest. Specifically, we identify the epidermal growth factor receptor as a target of S-nitrosylation, resulting in its retention within the endoplasmic reticulum and blockade of its receptor function. Overall, our findings highlight developmentally programmed S-nitrosylation as a critical mechanism that induces protein quality control in blood progenitors, maintaining their undifferentiated state by inhibiting cell-cycle progression and rendering them unresponsive to paracrine factors. Competing Interests: Declaration of interests The authors declare no competing interests. (Copyright © 2024 Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu