Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 119, Issue 6, Pages -Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.2111711119
Keywords
Yun; Prohibitin; intestinal stem cell; E2F1; Drosophila
Categories
Funding
- Beijing Municipal Commission of Education [KZ201910028040]
- National Natural Science Foundation of China [92054109, 31972893, 31471384]
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This study identifies Yun as a factor required for the proliferation of normal and transformed intestinal stem cells in adult Drosophila. Yun acts as a scaffold to stabilize the PHB complex and is regulated by EGFR/MAPK signaling. The Yun/PHB complex interacts with and positively affects the levels of E2F1 to regulate stem cell proliferation.
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 Drosophila 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.
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