Article ID Journal Published Year Pages File Type
1929894 Biochemical and Biophysical Research Communications 2012 7 Pages PDF
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.

► p53 downregulates IMPDH. ► p53-dependent miR-34a transactivation inhibits IMPDH transcription. ► miR-34a-mediated inhibition of IMPDH downregulates GTP-dependent Ras signal.

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Life Sciences Biochemistry, Genetics and Molecular Biology Biochemistry
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