# ist-1/IRS1  affects L1 starvation resistance in daf-16/FoxO- dependent and independent fashion

**Authors:** Jingxian Chen, Ainsley R. Scheiner, Ivan B. Falsztyn, L. Ryan Baugh

PMC · DOI: 10.17912/micropub.biology.001648 · 2025-06-13

## TL;DR

The study explores how the ist-1 gene in C. elegans affects resistance to starvation during early development, both through and independent of a known signaling pathway.

## Contribution

The study reveals that ist-1/IRS1 influences L1 starvation resistance via DAF-16/FoxO-dependent and -independent mechanisms.

## Key findings

- ist-1/IRS1 mutants show increased larval growth and reproduction after L1 starvation.
- ist-1/IRS1 promotes DAF-16 nuclear localization in starved larvae, suggesting involvement in insulin signaling.
- ist-1/IRS1 also functions independently of DAF-16/FoxO, indicating novel roles.

## Abstract

The mammalian IRS1 gene is an important adaptor for the insulin and insulin-like growth factor receptors, but its sole homolog in the nematode

C. elegans

,

ist-1

, has received relatively little attention. We show that

ist-1
/IRS1

has modest effects on L1 starvation resistance, with two null mutants increasing larval growth and reproduction after recovery from extended L1 arrest.

ist-1
/IRS1

mutants increase nuclear localization of
DAF-16
/FoxO, a critical effector of insulin/IGF signaling, in starved L1 larvae, consistent with
IST-1
/IRS1 transducing
DAF-2
/IGFR signaling. However, epistasis analysis suggests that

ist-1
/IRS1

also functions independently of

daf-16
/FoxO

, suggesting additional, novel function.

## Linked entities

- **Genes:** IST1 (IST1 factor associated with ESCRT-III) [NCBI Gene 9798], IRS1 (insulin receptor substrate 1) [NCBI Gene 3667], daf-16 (Forkhead box protein O) [NCBI Gene 172981], daf-2 (Insulin-like receptor subunit beta;Protein kinase domain-containing protein;receptor protein-tyrosine kinase) [NCBI Gene 175410]

## Full-text entities

- **Genes:** IRS1 (insulin receptor substrate 1) [NCBI Gene 3667] {aka HIRS-1}, IGF1R (insulin like growth factor 1 receptor) [NCBI Gene 3480] {aka CD221, IGFIR, IGFR, JTK13}, INS (insulin) [NCBI Gene 3630] {aka IDDM, IDDM1, IDDM2, ILPR, IRDN, MODY10}, IST1 (IST1 factor associated with ESCRT-III) [NCBI Gene 9798] {aka CHMP8, OLC1}
- **Species:** C. elegans [taxon 328850]

## Figures

1 figure with captions in the complete paper: https://tomesphere.com/paper/PMC12205376/full.md

---
Source: https://tomesphere.com/paper/PMC12205376