Abstract
Perturbed action of signal transduction pathways, including the mitogen-activated protein (MAP) kinase pathways, is one of the hallmarks of many cancers. While the implication of the typical MAP kinase pathways ERK1/2-MEK1/2, p38MAPK and JNK is well established, recent findings illustrate that the atypical MAP kinase ERK3/4-MK5 may also be involved in tumorigenic processes. Remarkably, the ERK3/4-MK5 pathway seems to possess anti-oncogenic as well as pro-oncogenic properties in cell culture and aninal models. This review summarizes the mutations in the genes encoding ERK3, ERK4 and MK5 that have been detected in different cancers, reports aberrant expression levels of these proteins in human tumours, and discusses the mechanisms by which this pathway can induce senescence, stimulate angiogenesis and invasiveness.
Highlights
Mitogen-activated protein kinase pathways The mitogen-activated protein kinase (MAPK) pathways play crucial roles in cell proliferation, differentiation, gene expression, apoptosis, metabolism and motility [1,2,3,4,5]
Pak3 mRNA levels, were downregulated upon induction of BRafV600E expression [60]. These results indicate that BRafV600E-induced transcriptional upregulation of the erk3 gene is independent of PAK3
In vitro studies and animal models demonstrate that the ERK3/4-MK5 pathway can participate in several processes that are dysregulated in cancer, including cell proliferation, cell motility, invasiveness, and angiogenesis
Summary
Mitogen-activated protein kinase pathways The mitogen-activated protein kinase (MAPK) pathways play crucial roles in cell proliferation, differentiation, gene expression, apoptosis, metabolism and motility [1,2,3,4,5]. (8) MK5-mediated phosphorylation of p53 at Ser-37 stimulates the transcriptional activity of p53, resulting in enhanced expression of p21Cip1. Elevated ERK3 levels result in G1 cell cycle arrest and inhibition of cell proliferation [22,42,43]. SiRNAmediated depletion of PCNA expression in several CML cell lines resulted in down-regulation of PAK2 and ERK3 transcript levels [56].
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