TY - JOUR
T1 - TAp63 is a master transcriptional regulator of lipid and glucose metabolism
AU - Su, Xiaohua
AU - Gi, Young Jin
AU - Chakravarti, Deepavali
AU - Chan, Io Long
AU - Zhang, Aijun
AU - Xia, Xuefeng
AU - Tsai, Kenneth Y.
AU - Flores, Elsa R.
N1 - Funding Information:
This work was supported by grants to E.R.F. from the American Cancer Society (RSG-07-082-01-MGO), the Mel Klein Foundation, and the Hildegardo E. and Olga M. Flores Foundation. This work was supported in part by NCI-R01 (R01CA160394), NCI-R01 (R01CA134796), and CPRIT (RP120124) to E.R.F., NCI-Cancer Center Core Grant (CA-16672) (University of Texas M.D. Anderson Cancer Center), and a Career Development Award from the Genitourinary Cancer SPORE (NCI CA091846). E.R.F. is a scholar of the Leukemia and Lymphoma Society of America, the Rita Allen Foundation, and the V Foundation for Cancer Research. D.C. was funded by a CPRIT training grant (RP101502). We would like to thank L.C.B. Chan, M.D. Saha, and P. Saha for scientific discussion and technical advice and the Mouse Metabolism Core at Baylor College of Medicine (funded by NIH P30 DK079638).
PY - 2012/10/3
Y1 - 2012/10/3
N2 - 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, AMPKα2, 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, AMPKα2, 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.
AB - 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, AMPKα2, 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, AMPKα2, 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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U2 - 10.1016/j.cmet.2012.09.006
DO - 10.1016/j.cmet.2012.09.006
M3 - Article
C2 - 23040072
AN - SCOPUS:84867094874
SN - 1550-4131
VL - 16
SP - 511
EP - 525
JO - Cell Metabolism
JF - Cell Metabolism
IS - 4
ER -