期刊
CELL METABOLISM
卷 16, 期 4, 页码 511-525出版社
CELL PRESS
DOI: 10.1016/j.cmet.2012.09.006
关键词
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资金
- American Cancer Society [RSG-07-082-01-MGO]
- Mel Klein Foundation
- Hildegardo E. and Olga M. Flores Foundation
- CPRIT [RP120124]
- NCI-Cancer Center Core Grant [CA-16672]
- Genitourinary Cancer SPORE [NCI CA091846]
- CPRIT training grant [RP101502]
- NIH [P30 DK079638]
- [NCI-R01 (R01CA160394)]
- [NCI-R01 (R01CA134796)]
TAp63 prevents premature aging, suggesting a link to genes that regulate longevity. Further characterization of TAp63-/- mice revealed that these mice develop obesity, insulin resistance, and glucose intolerance similar to those seen in mice lacking two key metabolic regulators, Silent information regulator T1 (Sirt1) and AMPK. While the roles of Sirt1 and AMPK in metabolism have been well studied, their upstream regulators are not well understood. We found that TAp63 is important in regulating energy metabolism by accumulating in response to metabolic stress and transcriptionally activating Sirt1, AMPK alpha 2, and LKB1, resulting in increased fatty acid synthesis and decreased fatty acid oxidation. Moreover, we found that TAp63 lowers blood glucose levels in response to metformin. Restoration of Sirt1, AMPK alpha 2, and LKB1 in TAp63-/- mice rescued some of the metabolic defects of the TAp63-/- mice. Our study defines a role for TAp63 in metabolism and weight control.
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