PKCζ Phosphorylates SIRT6 to Mediate Fatty Acid β-Oxidation in Colon Cancer Cells.

Protein kinase C has critical roles in regulating lipid anabolism and catabolism. a member of atypical family, has been reported to mediate glucose metabolism. However, whether and how regulates tumor cells fatty acid β-oxidation are unknown. Here, we report that the phosphorylation of SIRT6 is significantly increased after palmitic acid (PA) treatment in colon cancer cells. duanyu1531ζ can physically interact with SIRT6 in vitro and in vivo, and this interaction enhances following PA treatment. Further experiments show that duanyu1531ζ is the phosphorylase of SIRT6 and phosphorylates SIRT6 at threonine 294 residue to promote SIRT6 enrichment on chromatin. In the functional study, we find that the expression of ACSL1, CPT1, CACT, and HADHB, the genes related to fatty acid β-oxidation, increases after PA stimulation. We further confirm that duanyu1531ζ mediates the binding of SIRT6 specifically to the promoters of fatty acid β-oxidation-related genes and elicits the expression of these genes through SIRT6 phosphorylation. Our findings demonstrate the mechanism of duanyu1531ζ as a new phosphorylase of SIRT6 on maintaining tumor fatty acid β-oxidation and define the new role of duanyu1531ζ in lipid homeostasis.

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