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.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 FEBS+J
2015 ; 282
(4
): 613-29
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Feedforward regulation of mRNA stability by prolonged extracellular
signal-regulated kinase activity
#MMPMID25491268
Nagashima T
; Inoue N
; Yumoto N
; Saeki Y
; Magi S
; Volinsky N
; Sorkin A
; Kholodenko BN
; Okada-Hatakeyama M
FEBS J
2015[Feb]; 282
(4
): 613-29
PMID25491268
show ga
Extracellular signal-regulated kinase (ERK) plays a central role in signal
transduction networks and cell fate decisions. Sustained ERK activation induces
cell differentiation, whereas transient ERK results in the proliferation of
several types of cells. Sustained ERK activity stabilizes the proteins of
early-response gene products. However, the effect of ERK activity duration on
mRNA stability is unknown. We analyzed the quantitative relationship between the
duration of four ERK activity kinetics and the mRNA expression profile in growth
factor-treated cells. Time-course transcriptome analysis revealed that the cells
with prolonged ERK activity generally showed sustained mRNA expression of late
response genes but not early or mid genes. Selected late response genes decayed
more rapidly in the presence of a specific ERK inhibitor than a general
transcription inhibitor and the decay rate was not related to the number of
AU-rich elements. Our results suggest that sustained ERK activity plays an
important role in the lifespan of the mRNA encoded by late response genes, in
addition to the previously demonstrated role in protein stabilization of
early-response genes, including transcription factors regulating the
transcription of mid and late genes. This double-positive regulation of
ligand-induced genes, also termed feedforward regulation, is critical in cell
fate decisions.