Parsons Foundation. of cancer cells both in vitro and in vivo. In all, our results uncover a previously unidentified role of IKK in regulating glycolysis, sensing low-glutamine-induced metabolic stress, and promoting cellular adaptation to nutrient availability. panel) Wild-type, panel) Cells were lysed, and immunoblotting was performed with the indicated antibodies. (panel) Forty-eight hours after transfection, cells were cultured in glutamine-free medium, and viability was assessed by propodium iodide exclusion at the indicated time points. Data presented are mean SEM of three independent experiments performed in duplicate. (panel) Forty-eight hours after transfection, cells were lysed, and immunoblotting was performed with the indicated antibodies. (panel) Wild-type and panel) Cells were lysed, and immunoblotting was performed with the indicated antibodies. Data presented are mean SEM of three independent experiments performed in duplicate. (panel) HT1080 cells were transduced with control or p65 shRNA followed by puromycin selection, cells were cultured in complete or glutamine-free medium, and viability was assessed by propidium iodide exclusion at the indicated time KN-93 points. KN-93 Data presented are mean SEM of three independent experiments performed in duplicate. (panel) After puromycin selection, cells were lysed, and immunoblotting Rabbit Polyclonal to MLKL was performed with the indicated antibodies. (panel) Wild-type, panel) Cells were lysed, and immunoblotting was performed with the indicated antibodies. (***) 0.005, Student’s panel) PRISM structure analysis for the predicted interaction between IKK (Protein Data Bank [PDB]: 4KIK) and the IBCNFB complex (PDB: 1NFI). (panel) PRISM structure analysis for the predicted interaction between IKK (PDB: 4KIK) and PFKFB3 (PDB: 2DWO). ( 0.05; (***) 0.005, Student’s 0.05; (**) 0.01; (***) 0.005, Student’s 0.05; (**) 0.01; (***) 0.005, Student’s 0.05; (**) 0.01; (***) 0.005, Student’s 0.05 [*], 0.01 [**], and 0.005 [***]). Supplementary Material Supplemental Material: Click here to view. Acknowledgments We thank members of the Kong laboratory for helpful comments on the manuscript. We thank Ross Tomaino at the Harvard Mass Spectrometry Core for assisting in the protein mass spectrometric peptide sequencing and phosphopeptide mapping experiments. Research is supported by National Institutes of Health/National Cancer Institute 1R01CA183989-01A1. M.A.R. is supported by the Ralph M. Parsons Foundation. M.K. is the Pew Scholar in the Biomedical Sciences, V Scholar in Cancer Research, and American Cancer Society Research Scholar. X.H.L. is supported by DNA Damage Response and Oncogenic Signaling (DDROS) Training Program KN-93 at City of Hope. Research reported here includes work performed in Core Facilities supported by the National Institutes of Health/National Cancer Institute under grant number P30CA33572. Footnotes Supplemental material is available for this article. Article published online ahead of print. Article and publication date KN-93 are online at http://www.genesdev.org/cgi/doi/10.1101/gad.287235.116..