PKCζ Phosphorylates SIRT6 to Mediate Fatty Acid β-Oxidation in Colon Cancer Cells
Protein kinase C (PKC) has critical roles in regulating lipid anabolism and catabolism. PKCζ, a member of atypical PKC family, has been reported to mediate glucose metabolism. However, whether and how PKCζ regulates tumor cells fatty acid β-oxidation are unknown. Here, we report that the phosphoryla...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2019-01-01
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| Series: | Neoplasia: An International Journal for Oncology Research |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1476558618303130 |
| _version_ | 1818597210563018752 |
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| author | Tian Gao Meiting Li Guanqun Mu Tianyun Hou Wei-Guo Zhu Yang Yang |
| author_facet | Tian Gao Meiting Li Guanqun Mu Tianyun Hou Wei-Guo Zhu Yang Yang |
| author_sort | Tian Gao |
| collection | DOAJ |
| description | Protein kinase C (PKC) has critical roles in regulating lipid anabolism and catabolism. PKCζ, a member of atypical PKC family, has been reported to mediate glucose metabolism. However, whether and how PKCζ 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. PKCζ can physically interact with SIRT6 in vitro and in vivo, and this interaction enhances following PA treatment. Further experiments show that PKCζ 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 PKCζ 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 PKCζ as a new phosphorylase of SIRT6 on maintaining tumor fatty acid β-oxidation and define the new role of PKCζ in lipid homeostasis. |
| first_indexed | 2024-12-16T11:44:11Z |
| format | Article |
| id | doaj.art-247a5b2d76bc4e6997238c4e836e3bfb |
| institution | Directory Open Access Journal |
| issn | 1476-5586 |
| language | English |
| last_indexed | 2024-12-16T11:44:11Z |
| publishDate | 2019-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neoplasia: An International Journal for Oncology Research |
| spelling | doaj.art-247a5b2d76bc4e6997238c4e836e3bfb2022-12-21T22:32:52ZengElsevierNeoplasia: An International Journal for Oncology Research1476-55862019-01-012116173PKCζ Phosphorylates SIRT6 to Mediate Fatty Acid β-Oxidation in Colon Cancer CellsTian Gao0Meiting Li1Guanqun Mu2Tianyun Hou3Wei-Guo Zhu4Yang Yang5Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Peking University Health Science Center, 38 Xueyuan Road, Beijing 100191, ChinaDepartment of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Peking University Health Science Center, 38 Xueyuan Road, Beijing 100191, ChinaDepartment of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Peking University Health Science Center, 38 Xueyuan Road, Beijing 100191, ChinaDepartment of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Peking University Health Science Center, 38 Xueyuan Road, Beijing 100191, ChinaDepartment of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Peking University Health Science Center, 38 Xueyuan Road, Beijing 100191, China; Guangdong Key Laboratory for Genome Stability and Human Disease Prevention, Department of Biochemistry and Molecular Biology, School of Medicine, Shenzhen University, Shenzhen 516080, ChinaDepartment of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Peking University Health Science Center, 38 Xueyuan Road, Beijing 100191, China; Address all correspondence to: Yang Yang, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Peking University Health Science Center, #38 Xueyuan Road, Beijing 100191, China.Protein kinase C (PKC) has critical roles in regulating lipid anabolism and catabolism. PKCζ, a member of atypical PKC family, has been reported to mediate glucose metabolism. However, whether and how PKCζ 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. PKCζ can physically interact with SIRT6 in vitro and in vivo, and this interaction enhances following PA treatment. Further experiments show that PKCζ 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 PKCζ 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 PKCζ as a new phosphorylase of SIRT6 on maintaining tumor fatty acid β-oxidation and define the new role of PKCζ in lipid homeostasis.http://www.sciencedirect.com/science/article/pii/S1476558618303130 |
| spellingShingle | Tian Gao Meiting Li Guanqun Mu Tianyun Hou Wei-Guo Zhu Yang Yang PKCζ Phosphorylates SIRT6 to Mediate Fatty Acid β-Oxidation in Colon Cancer Cells Neoplasia: An International Journal for Oncology Research |
| title | PKCζ Phosphorylates SIRT6 to Mediate Fatty Acid β-Oxidation in Colon Cancer Cells |
| title_full | PKCζ Phosphorylates SIRT6 to Mediate Fatty Acid β-Oxidation in Colon Cancer Cells |
| title_fullStr | PKCζ Phosphorylates SIRT6 to Mediate Fatty Acid β-Oxidation in Colon Cancer Cells |
| title_full_unstemmed | PKCζ Phosphorylates SIRT6 to Mediate Fatty Acid β-Oxidation in Colon Cancer Cells |
| title_short | PKCζ Phosphorylates SIRT6 to Mediate Fatty Acid β-Oxidation in Colon Cancer Cells |
| title_sort | pkcζ phosphorylates sirt6 to mediate fatty acid β oxidation in colon cancer cells |
| url | http://www.sciencedirect.com/science/article/pii/S1476558618303130 |
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