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

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.

journal_name

Biochem Biophys Res Commun

journal_title

Biochemical and biophysical research communications

authors

Kim HR,Roe JS,Lee JE,Hwang IY,Cho EJ,Youn HD

doi

10.1016/j.bbrc.2012.01.077

subject

Has Abstract

pub_date

2012-02-24 00:00:00

pages

682-8

issue

4

eissn

0006-291X

issn

1090-2104

pii

S0006-291X(12)00111-8

journal_volume

418

pub_type

杂志文章

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