What is it about?
Cancer cells are characterized by a high rate of fatty acid synthesis required for membrane expansion during rapid proliferation. As a key rate limiting enzyme in de novo fatty acid synthesis, ACLY is frequently deregulated by PTMs in tumors. Despite recently identified O-GlcNAcylation on ACLY, its biological function is still unknown. Here, we identify ACLY S979 as a key O-GlcNAcylation site that is crucial for ACLY function. By improving CoA association, S979 O-GlcNAcylation enhances ACLY activity and in turn promotes lipogenesis and tumor cell proliferation. Also, it is capable of sensing nutritional alterations and EGF stimulation and fine-tunes fatty acid synthesis accordingly. Together, this work brings insights into the dynamic coordination between glucose supply and lipogenesis for rapid tumor cell proliferation.
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This page is a summary of: O
-GlcNAcylation of ATP-citrate lyase couples glucose supply to lipogenesis for rapid tumor cell proliferation, Proceedings of the National Academy of Sciences, October 2024, Proceedings of the National Academy of Sciences,
DOI: 10.1073/pnas.2402674121.
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