Repression of Akt3 gene transcription by the tumor suppressor RIZ1

Qingnan Liu1,2, Xiaotian Qu1, Xiaolei Xie1

  • 1Center for Medical Genetics, School of Life Sciences, Central South University, Changsha, Hunan, China.

Scientific Reports
|January 26, 2018
PubMed

Insights

RIZ1 (PR domain zinc finger protein 1) acts as a tumor suppressor and regulates Akt3 expression. This research reveals RIZ1

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Metabolic Diseases

Background:

  • RIZ1 is implicated as a tumor suppressor in metabolic diseases like obesity and cancer.
  • The Akt pathway is crucial in both cancer and obesity, with a known link to RIZ1.

Purpose of the Study:

  • To investigate the regulatory role of RIZ1 in the expression of Akt3.
  • To elucidate the molecular mechanisms underlying RIZ1's influence on the Akt pathway in the context of cancer and obesity.

Main Methods:

  • Overexpression of RIZ1 in HEK293 cells.
  • Luciferase reporter assays to assess Akt3 promoter activity.
  • In vitro binding assays with recombinant RIZ1 and the Akt3 promoter.
  • Chromatin immunoprecipitation (ChIP) assays to confirm in vivo binding.
  • Analysis of H3K9 methylation on the Akt3 promoter.

Main Results:

  • Overexpression of RIZ1 led to reduced Akt3 protein levels.
  • RIZ1 significantly repressed Akt3 gene promoter activity.
  • RIZ1 directly binds to the Akt3 promoter both in vitro and in vivo.
  • RIZ1 overexpression increased H3K9 methylation at the Akt3 promoter.

Conclusions:

  • Akt3 is identified as a direct transcriptional target of RIZ1.
  • RIZ1-mediated regulation of Akt3 contributes to understanding the Akt pathway in cancer and obesity.
  • This study expands knowledge on RIZ1's function in metabolic and oncogenic processes.

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