CREB regulated transcriptional coactivators (CRTCs) are a family of transcriptional cofactors involved in diverse physiological processes including energy homeostasis, learning and memory, mitochondrial biogenesis, fat metabolism and ER stress. CRTCs are direct targets of AMPK and their aberrant regulation is causal to multiple complex diseases associated with food intake including diabetes, cancer and human obesity. CRTC were discovered in mammals due to their regulation of CREB transcription, but subsequently shown to bind to and regulate multiple bZIP transcription factors. We identified the single C. elegans CRTC family member, ‘CRTC-1’, which is inactivated by low nutrients. CRTC-1 acts as a longevity switch downstream of AMPK – the positive effects of AMPK on healthy aging require its ability to regulate CRTC-1 activity. We continue to explore novel roles for CRTCs in both aging and age-related diseases, in addition to how they impact broader cellular and organismal metabolism.
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Mair W, Morantte I, Rodrigues AP, Manning G, Montminy M, Shaw RJ, Dillin A.
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