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000285025 1001_ $$0P:(DE-2719)9002963$$aNiedworok, Patrizia$$b0$$eFirst author$$udzne
000285025 245__ $$aBCL-11 enables adaptive stress responses to environmental challenges.
000285025 260__ $$aSt. Louis$$bElsevier$$c2026
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000285025 520__ $$aInsulin/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.
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000285025 650_7 $$2Other$$abiological sciences
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000285025 7001_ $$0P:(DE-2719)9002528$$aCiliberti, Rossella Erminia$$b1$$udzne
000285025 7001_ $$0P:(DE-2719)9001936$$aXie, Beijia$$b2$$udzne
000285025 7001_ $$0P:(DE-2719)9002538$$aMathew, Amal John$$b3$$udzne
000285025 7001_ $$0P:(DE-HGF)0$$aJussila, Benjamin$$b4
000285025 7001_ $$0P:(DE-HGF)0$$aLawson, Jennifer A$$b5
000285025 7001_ $$0P:(DE-2719)9000846$$aDe Domenico, Elena$$b6$$udzne
000285025 7001_ $$0P:(DE-2719)9002116$$aPaulusch, Stefan$$b7$$udzne
000285025 7001_ $$0P:(DE-2719)2812219$$aBeyer, Marc$$b8$$udzne
000285025 7001_ $$0P:(DE-2719)2010732$$aNicotera, Pierluigi$$b9$$udzne
000285025 7001_ $$0P:(DE-2719)2812578$$aAziz, N Ahmad$$b10$$udzne
000285025 7001_ $$0P:(DE-2719)2289209$$aEhninger, Dan$$b11$$udzne
000285025 7001_ $$0P:(DE-HGF)0$$aBlaess, Sandra$$b12
000285025 7001_ $$0P:(DE-2719)2158358$$aBano, Daniele$$b13$$eLast author$$udzne
000285025 773__ $$0PERI:(DE-600)2927064-9$$a10.1016/j.isci.2025.114422$$gVol. 29, no. 2, p. 114422 -$$n2$$p114422$$tiScience$$v29$$x2589-0042$$y2026
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