E-GEOD-4739 - Transcription profiling of mouse NIH3T3 cell line cultured with and withput FGF and treated with the MEK Inhibitor U0126 at 3 time points before FGF addition reveals ERK-dependent downregulated genes have the ability to block S phase entry
Submitted on 28 April 2006, released on 24 November 2007, last updated on 27 March 2012
The ERK family of MAP kinase plays a critical role in growth factor-stimulated cell cycle progression from G0/G1 to S phase. But, how sustained activation of ERK promotes G1 progression has remained unclear. Here, our systematic analysis on the temporal program of ERK-dependent gene expression shows that sustained activation of ERK is required for induction and maintenance of the decreased expression levels of a set of genes. Moreover, our cell biological analysis reveals that these ERK-dependent downregulated genes have the ability to block S phase entry. Cessation of ERK activation at mid or late G1 leads to a rapid increase of these anti-proliferative genes and results in the inhibition of S phase entry. These findings uncover an important mechanism by which the duration of ERK activation regulates cell cycle progression through dynamic changes in gene expression, and identify novel ERK target genes crucial for the regulation of cell cycle progression.
transcription profiling by array, co-expression, growth condition, time series
Continuous ERK activation downregulates antiproliferative genes throughout G1 phase to allow cell-cycle progression. Takuya Yamamoto, Miki Ebisuya, Fumito Ashida, Kazuo Okamoto, Shin Yonehara, Eisuke Nishida. Curr Biol 16(12):1171-82 (2006)