The Yun/Prohibitin complex regulates adult Drosophila intestinal stem cell proliferation through the transcription factor E2F1

Stem cells constantly divide and differentiate to maintain adult tissue homeostasis, and uncontrolled stem cell proliferation leads to severe diseases such as cancer. How stem cell proliferation is precisely controlled remains poorly understood. Here, from an RNA interference (RNAi) screen in adult...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2022-02, Vol.119 (6), p.1
Main Authors: Zhao, Hang, Shi, Lin, Li, Zhengran, Kong, Ruiyan, Ren, Xuejing, Ma, Rui, Jia, Lemei, Ma, Meifang, Lu, Shan, Xu, Ran, Binari, Richard, Wang, Jian-Hua, Dong, Meng-Qiu, Perrimon, Norbert, Li, Zhouhua
Format: Article
Language:English
Subjects:
Adult Stem Cells - metabolism
Animals
Animals, Genetically Modified
Biological Sciences
Cell differentiation
Cell Differentiation - physiology
Cell growth
Cell proliferation
Cell Proliferation - physiology
Drosophila
Drosophila melanogaster - metabolism
Drosophila Proteins - metabolism
E2F1 Transcription Factor - metabolism
Fruit flies
Gene expression
Homeostasis
Homeostasis - physiology
Insects
Intestine
Intestines - metabolism
MAP kinase
Progenitor cells
Prohibitin
Prohibitins - metabolism
RNA Interference - physiology
RNA-mediated interference
Signal Transduction - physiology
Stem cells
Transcription factors
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Summary:Stem cells constantly divide and differentiate to maintain adult tissue homeostasis, and uncontrolled stem cell proliferation leads to severe diseases such as cancer. How stem cell proliferation is precisely controlled remains poorly understood. Here, from an RNA interference (RNAi) screen in adult intestinal stem cells (ISCs), we identify a factor, Yun, required for proliferation of normal and transformed ISCs. Yun is mainly expressed in progenitors; our genetic and biochemical evidence suggest that it acts as a scaffold to stabilize the Prohibitin (PHB) complex previously implicated in various cellular and developmental processes and diseases. We demonstrate that the Yun/PHB complex is regulated by and acts downstream of EGFR/MAPK signaling. Importantly, the Yun/PHB complex interacts with and positively affects the levels of the transcription factor E2F1 to regulate ISC proliferation. In addition, we find that the role of the PHB complex in cell proliferation is evolutionarily conserved. Thus, our study uncovers a Yun/PHB-E2F1 regulatory axis in stem cell proliferation.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.2111711119