Abstract
The p38 mitogen-activated protein kinase (p38MAPK) pathway has been implicated in a variety of pathological conditions including inflammation and metastasis. Post-transcriptional regulation of genes harboring adenine/uridine-rich elements (AREs) in their 3′-untranslated region (3′-UTR) is controlled by MAPK-activated protein kinase 2 (MAPKAPK2 or MK2), a downstream substrate of the p38MAPK. In response to diverse extracellular stimuli, MK2 influences crucial signaling events, regulates inflammatory cytokines, transcript stability and critical cellular processes. Expression of genes involved in these vital cellular cascades is controlled by subtle interactions in underlying molecular networks and post-transcriptional gene regulation that determines transcript fate in association with RNA-binding proteins (RBPs). Several RBPs associate with the 3′-UTRs of the target transcripts and regulate their expression via modulation of transcript stability. Although MK2 regulates important cellular phenomenon, yet its biological significance in tumor progression has not been well elucidated till date. In this review, we have highlighted in detail the importance of MK2 as the master regulator of RBPs and its role in the regulation of transcript stability, tumor progression, as well as the possibility of use of MK2 as a therapeutic target in tumor management.
Highlights
A variety of stimuli evokes specific responses in cells via p38 mitogen-activated protein kinase (p38MAPK) signal pathway activation
The stress-activated p38MAPK signaling pathway regulates a plethora of cellular processes in particular apoptosis, cell division, cell invasion, and inflammatory response [1]. p38MAPK pathway’s downstream substrate, mitogen-activated protein kinase-activated protein kinase 2 (MAPKAPK2 or Mitogen-activated protein kinase-activated protein kinase 2 (MK2)) is involved in the post-translational regulation of cytokines as evident in MK2 knockout (MK2−/−) mice showing attenuated production of tumor necrosis factor (TNFα) protein when compared to wild-type mice
Experimental evidence indicates that MK2, the prime target of p38MAPK, regulates the stability of essential genes involved in tumor pathogenesis that harbour adenine/uridine-rich elements (AREs) in their 3′-untranslated region (3′-Untranslated region (UTR)) [8]
Summary
A variety of stimuli evokes specific responses in cells via p38 mitogen-activated protein kinase (p38MAPK) signal pathway activation. It is quite evident that MK2 is the prime downstream substrate of p38MAPK, and this signaling cascade regulates the stability and translation of TNFα and IL-6 mRNAs through AREs involvement in the 3′-UTRs of these transcripts (Fig. 4).
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