PMID: 9190899Jun 12, 1997Paper

Myc represses the growth arrest gene gadd45

Oncogene
W W MarhinLinda Z Penn

Abstract

The c-Myc protein strongly stimulates cellular proliferation, inducing cells to exit G0/G1 and enter the cell cycle. At a molecular level, Myc prevents growth arrest and drives cell cycle progression through the transcriptional regulation of Myc-target genes. Expression of the growth arrest and DNA damage inducible gene 45 (gadd45) is elevated in response to DNA damaging agents, such as ionizing radiation via a p53-dependent mechanism, upon nutrient deprivation, or during differentiation. Gadd45 holds a vital role in growth arrest as ectopic expression confers a strong block to proliferation. Exposure of quiescent cells to mitogen stimulates a rapid increase in c-Myc expression which is followed by the subsequent reduction in gadd45 expression. The kinetics of these two regulatory events suggest that Myc suppresses the expression of gadd45, contributing to G0/G1 phase exit of the cell cycle. Indeed, ectopic Myc expression in primary and immortalized fibroblasts results in the suppression of gadd45 mRNA levels, by a mechanism which is independent of cell cycle progression. Using an inducible MycER system, rapid suppression of gadd45 mRNA is first evident approximately 0.5 h following Myc activation. The reduction in gadd45 mRNA ...Continue Reading

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