Glucose tolerance in mice is linked to the dose of the p53 transactivation domain

Debra Franck, Laura Tracy, Heather L. Armata, Christine L. Delaney, Dae Young Jung, Hwi Jin Ko, Helena Ong, Jason K. Kim, Heidi Scrable, Hayla K. Sluss

Research output: Contribution to journalArticle

14 Scopus citations

Abstract

Aim. To test the transactivation domain-mediated control of glucose homeostasis by the tumor suppressor p53. Background. The tumor suppressor p53 has a critical role in maintenance of glucose homeostasis. Phosphorylation of Ser18 in the transaction domain of p53 controls the expression of Zpf385a, a zinc finger protein that regulates adipogenesis and adipose function. This results suggest that the transactivation domain of p53 is essential to the control of glucose homeostasis. Materials and Methods. Mice with mutations in the p53 transactivation domain were examined for glucose homeostasis as well as various metabolic parameters. Glucose tolerance and insulin tolerance tests were performed on age matched wild type and mutant animals. In addition, mice expressing increased dosage of p53 were also examined. Results. Mice with a mutation in p53Ser18 exhibit reduced Zpf385a expression in adipose tissue, adipose tissue-specific insulin resistance, and glucose intolerance. Mice with relative deficits in the transactivation domain of p53 exhibit similar defects in glucose homeostasis, while "Super p53" mice with an increased dosage of p53 exhibit improved glucose tolerance. Conclusion. These data support the role of an ATM - p53 cellular stress axis that helps combat glucose intolerance and insulin resistance and regulates glucose homeostasis.

Original languageEnglish (US)
Pages (from-to)139-150
Number of pages12
JournalEndocrine Research
Volume38
Issue number3
DOIs
StatePublished - Jul 4 2013

Keywords

  • Glucose intolerance
  • Mouse genetics
  • P53

ASJC Scopus subject areas

  • Endocrinology

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    Franck, D., Tracy, L., Armata, H. L., Delaney, C. L., Jung, D. Y., Ko, H. J., Ong, H., Kim, J. K., Scrable, H., & Sluss, H. K. (2013). Glucose tolerance in mice is linked to the dose of the p53 transactivation domain. Endocrine Research, 38(3), 139-150. https://doi.org/10.3109/07435800.2012.735735