A p53-inducible microRNA-34a downregulates Ras signaling by targeting IMPDH

Hwa Ryeon Kim, Jae Seok Roe, Ji Eun Lee, In Young Hwang, Eun Jung Cho, Hong Duk Youn

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

p53 is a well-known transcription factor that controls cell cycle arrest and cell death in response to a wide range of stresses. Moreover, p53 regulates glucose metabolism and its mutation results in the metabolic switch to the Warburg effect found in cancer cells. Nucleotide biosynthesis is also critical for cell proliferation and the cell division cycle. Nonetheless, little is known about whether p53 regulates nucleotide biosynthesis. Here we demonstrated that p53-inducible microRNA-34a (miR-34a) repressed inosine 5'-monophosphate dehydrogenase (IMPDH), a rate-limiting enzyme of de novo GTP biosynthesis. Treatment with anti-miR-34a inhibitor relieved the expression of IMPDH upon DNA damage. Ultimately, miR-34a-mediated inhibition of IMPDH resulted in repressed activation of the GTP-dependent Ras signaling pathway. In summary, we suggest that p53 has a novel function in regulating purine biosynthesis, aided by miR-34a-dependent IMPDH repression.

Original languageEnglish
Pages (from-to)682-688
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume418
Issue number4
DOIs
Publication statusPublished - 2012 Feb 24

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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