MAPK pathways are well-studied regulatory elements linked to the regulation of nuclear gene expression by its interaction with transcription factors. An additional and equally interesting level of control of gene expression is provided by mechanisms that control mRNA stability. Our results indicate that while ERK2 promotes fos gene transcription, another MAPK (p38 MAPK) regulates fos mRNA decay by affecting the state of phosphorylation of specific mRNA binding proteins. In this fashion, concerted early (ERK) or late (p38) MAPK activation can contribute to both rapid and transient activation of the early responsive gene fos.
- stability of mRNAs
- p38 MAPKs
Abbreviations: AP-1, activator protein 1; APRIL, acidic leucine-rich nuclear phosphoprotein 32 family member B, ANP32B; ARE, AU-rich element; AUBP, AU-rich binding protein; Bi–RNA, 5′-end biotin-labelled RNA oligonucleotide; DMEM, Dulbecco's modified Eagle's medium; EGF, epidermal growth factor; EMSA, electrophoretic mobility-shift assay; ERK, extracellular-signal-regulated kinase; GAPDH, glyceraldehyde-3-phosphate dehydrogenase; HA, haemagglutinin; HEK, human embryonic kidney; HuR, Hu-antigen 1, Elav-like protein 1, ELAVL1; IEG, immediate-early responsive gene; iNOS, inducible nitric oxide synthase, NOS2; JNK, c-Jun N-terminal kinase; KSRP, far upstream element-binding protein 2, KHSRP; Luc, luciferase; MAPK, mitogen-activated protein kinase; MAPKK, mitogen-activated protein kinase kinase; MK2, mitogen-activated protein kinase-activated protein kinase 2; PDGF, platelet-derived growth factor; PEI, polyethyleneimine; PK, proteinase K; PP, protein phosphatase; PPI, protein–protein interaction; qPCR, quantitative PCR; TNF, tumour necrosis factor; TTP, tristetraprolin, ZFP36; UTR, untranslated region; WT, wild-type
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