生物
造血
细胞生物学
果蝇属(亚属)
未折叠蛋白反应
S-亚硝基化
祖细胞
干细胞
遗传学
基因
内质网
生物化学
半胱氨酸
酶
作者
Bumsik Cho,Min-Kyo Shin,Eun‐Ju Chang,Sang Jun Son,Incheol Shin,Jiwon Shim
标识
DOI:10.1016/j.devcel.2024.02.013
摘要
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.
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