TY  - JOUR
AU  - Niedworok, Patrizia
AU  - Ciliberti, Rossella Erminia
AU  - Xie, Beijia
AU  - Mathew, Amal John
AU  - Jussila, Benjamin
AU  - Lawson, Jennifer A
AU  - De Domenico, Elena
AU  - Paulusch, Stefan
AU  - Beyer, Marc
AU  - Nicotera, Pierluigi
AU  - Aziz, N Ahmad
AU  - Ehninger, Dan
AU  - Blaess, Sandra
AU  - Bano, Daniele
TI  - BCL-11 enables adaptive stress responses to environmental challenges.
JO  - iScience
VL  - 29
IS  - 2
SN  - 2589-0042
CY  - St. Louis
PB  - Elsevier
M1  - DZNE-2026-00150
SP  - 114422
PY  - 2026
AB  - 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.
KW  - biological sciences (Other)
KW  - cell biology (Other)
KW  - health sciences (Other)
KW  - molecular biology (Other)
LB  - PUB:(DE-HGF)16
C6  - pmid:41641102
C2  - pmc:PMC12865584
DO  - DOI:10.1016/j.isci.2025.114422
UR  - https://pub.dzne.de/record/285025
ER  -