Neuronal IL-17 controls Caenorhabditis elegans developmental diapause through CEP-1/p53

• 成果类型: Article
• 署名作者: Godthi, Abhishiktha; Min, Sehee; Das, Srijit; Corchado, Johnny Cruz-; Deonarine, Andrew; Misel-Wuchter, Kara; Issuree, Priya D.; Prahlad, Veena
• 署名单位: Roswell Park Comprehensive Cancer Center; University of Iowa; University of Iowa
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-9351
• DOI: 10.1073/pnas.2315248121
• 发表日期: 2024-03-11
• 关键词: c-elegans; dauer formation; life-span; tumor-suppressor; p53; plasticity; apoptosis; nematode; stress; daf-16

摘要

During metazoan development, how cell division and metabolic programs are coordinated with nutrient availability remains unclear. Here, we show that nutrient availability signaled by the neuronal cytokine, ILC- 17.1, switches Caenorhabditis elegans development between reproductive growth and dormancy by controlling the activity of the tumor suppressor p53 ortholog, CEP- 1. Specifically, upon food availability, ILC- 17.1 signaling by amphid neurons promotes glucose utilization and suppresses CEP- 1/p53 to allow growth. In the absence of ILC- 17.1, CEP- 1/p53 is activated, up- regulates cell- cycle inhibitors, decreases phosphofructokinase and cytochrome C expression, and causes larvae to arrest as stress- resistant, quiescent dauers. We propose a model whereby ILC- 17.1 signaling links nutrient availability and energy metabolism to cell cycle progression through CEP- 1/p53. These studies describe ancestral functions of IL- 17 s and the p53 family of proteins and are relevant to our understanding of neuroimmune mechanisms in cancer. They also reveal a DNA damage-independent function of CEP- 1/p53 in invertebrate development and support the existence of a previously undescribed C. elegans dauer pathway.