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Journal of Genetics and Genomics

Journal of Genetics and Genomics

IF: 6.6
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Derlin-1 and TER94/VCP/p97 are required for intestinal homeostasis

Published:1 March 2022 DOI: 10.1016/j.jgg.2021.08.017 PMID: 34547438
Fuli Liu , Hang Zhao , Ruiyan Kong , Lin Shi , Zhengran Li , Rui Ma , Huiqing Zhao , Zhouhua Li

Abstract

Adult stem cells are critical for the maintenance of residential tissue homeostasis and functions. However, the roles of cellular protein homeostasis maintenance in stem cell proliferation and tissue homeostasis are not fully understood. Here, we find that Derlin-1 and TER94/VCP/p97, components of the endoplasmic reticulum (ER)-associated degradation (ERAD) pathway, restrain intestinal stem cell proliferation to maintain intestinal homeostasis in adult Drosophila. Depleting any of them results in increased stem cell proliferation and midgut homeostasis disruption. Derlin-1 is specifically localized in the ER of progenitors, and its C-terminus is required for its function. Interestingly, we find that increased stem cell proliferation is resulted from elevated ROS levels and activated JNK signaling in Derlin-1- or TER94-deficient progenitors. Further removal of reactive oxygen species (ROS) or inhibition of JNK signaling almost completely suppresses increased stem cell proliferation. Together, these data demonstrate that the ERAD pathway is critical for stem cell proliferation and tissue homeostasis. Thus, we provide insights into our understanding of the mechanisms underlying cellular protein homeostasis maintenance (ER protein quality control) in tissue homeostasis and tumor development.

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Materials
Procduct Name CAS Molecular Formula Supplier Price
LY-364947 396129-53-6 C17H12N4 187 suppliers $9.00-$20620.00
LY-364947 396129-53-6 C17H12N4 187 suppliers $9.00-$20620.00
LY-364947 396129-53-6 C17H12N4 187 suppliers $9.00-$20620.00
LY-364947 396129-53-6 C17H12N4 187 suppliers $9.00-$20620.00

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