# BCL-11 enables adaptive stress responses to environmental challenges **Authors:** Patrizia Niedworok, Rossella Erminia Ciliberti, Beijia Xie, Amal John Mathew, Benjamin Jussila, Jennifer A. Lawson, Elena De Domenico, Stefan Paulusch, Marc Beyer, Pierluigi Nicotera, N. Ahmad Aziz, Dan Ehninger, Sandra Blaess, Daniele Bano PMC · DOI: 10.1016/j.isci.2025.114422 · iScience · 2026-01-07 ## TL;DR This study explores how BCL-11 interacts with insulin signaling to help worms respond to stress and maintain cell health. ## Contribution The study reveals a novel role for BCL-11 in modulating stress resilience through its interaction with insulin/IGF-1 signaling in C. elegans. ## Key findings - BCL-11 deficiency impairs the protective effects of daf-2 signaling during stress. - DAF-16 loss rescues developmental defects in daf-2;bcl-11 mutants. - BCL-11 is involved in stress resilience in adult worms. ## Abstract Insulin/IGF-1 signaling (IIS) is a master regulator of metabolism, stress resilience, and cell homeostasis in multicellular organisms. In the nematode Caenorhabditis elegans, DAF-2 regulates dauer diapause, animal growth, and lifespan extension in a DAF-16/FOXO-dependent manner. Here we investigated IIS in animals expressing pathogenic variants of BCL-11, an evolutionarily conserved transcription factor that has been implicated in human neurodevelopmental disorders. We found that hypomorphic bcl-11 mutations have a limited impact on C. elegans growth and survival under standard growth conditions. On the contrary, BCL-11 deficiency compromises the cytoprotective properties of daf-2 signaling upon animal exposure to stress. During embryonic development, daf-16 loss of function rescues egg hatching defects in daf-2;bcl-11 mutants, suggesting a transcriptional interplay between BCL-11 and DAF-16 in IIS-deficient animals. Together, our data suggest that BCL-11 actively regulates transcription during development, while in adult animals it is recruited in response to environmental insults to enhance stress resilience. •Hypomorphic bcl-11 mutants do not show obvious phenotypes•daf-2;bcl-11 mutants display altered transcriptional profiles under stress•DAF-16 loss rescues developmental defects in daf-2;bcl-11-mutant animals•BCL-11 deficiency impairs the cytoprotective properties of daf-2 signaling Hypomorphic bcl-11 mutants do not show obvious phenotypes daf-2;bcl-11 mutants display altered transcriptional profiles under stress DAF-16 loss rescues developmental defects in daf-2;bcl-11-mutant animals BCL-11 deficiency impairs the cytoprotective properties of daf-2 signaling Health sciences; Biological sciences; Molecular biology; Cell biology ## Linked entities - **Genes:** bcl-11 (C2H2-type domain-containing protein) [NCBI Gene 179019], daf-2 (Insulin-like receptor subunit beta;Protein kinase domain-containing protein;receptor protein-tyrosine kinase) [NCBI Gene 175410], daf-16 (Forkhead box protein O) [NCBI Gene 172981] - **Species:** Caenorhabditis elegans (taxon 6239) ## Full-text entities - **Genes:** daf-2 (Insulin-like receptor subunit beta;Protein kinase domain-containing protein;receptor protein-tyrosine kinase) [NCBI Gene 175410], bcl-11 (C2H2-type domain-containing protein) [NCBI Gene 179019], daf-16 (Forkhead box protein O) [NCBI Gene 172981] - **Diseases:** neurodevelopmental disorders (MESH:D002658), IIS (MESH:C564816) - **Species:** C. elegans [taxon 328850], Caenorhabditis elegans (species) [taxon 6239], Homo sapiens (human, species) [taxon 9606] ## Full text _Full body text omitted from this summary view._ Fetch the complete paper as Markdown: https://tomesphere.com/paper/PMC12865584/full.md ## Figures 5 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12865584/full.md ## References 58 references — full list in the complete paper: https://tomesphere.com/paper/PMC12865584/full.md --- Source: https://tomesphere.com/paper/PMC12865584