Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.11.24 (mitogen-activated protein kinase)
 95,810 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

RNA regulators are critical for animal development, especially in the germ line where gene expression is often modulated by changes in mRNA stability, translation, and localization. In this paper, we focus on Caenorhabditis elegans LARP-1, a representative of one La-related protein (Larp) family found broadly among eukaryotes. LARP-1 possesses a signature La motif, which is an ancient RNA-binding domain, plus a second conserved motif, typical of LARP-1 homologs and therefore dubbed the LARP1 domain. LARP-1 appears to bind RNA in vitro via both the La motif and the LARP1 domain. larp-1 null mutants have an oogenesis defect reminiscent of hyperactive Ras-MAPK signaling; this defect is suppressed or enhanced by down- or up-regulating the Ras-MAPK pathway, respectively. Consistent with a role in down-regulating the Ras-MAPK pathway, larp-1 null mutants have higher than normal levels of selected pathway mRNAs and proteins. LARP-1 protein colocalizes with P bodies, which function in RNA degradation. We suggest that LARP-1 functions in P bodies to attenuate the abundance of conserved Ras-MAPK mRNAs. We also propose that the cluster of LARP-1 homologs may function generally to control the expression of key developmental regulators.
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PMID:C. elegans La-related protein, LARP-1, localizes to germline P bodies and attenuates Ras-MAPK signaling during oogenesis. 1851 47

The Ras-ERK/MAP (Mitogen-Activated Protein) kinase signaling pathway governs many cellular processes such as proliferation, differentiation, cell fate, homeostasis, and survival in all eukaryotes. Constitutive activation of the Ras-ERK/MAPK signaling pathway often leads to promotion of abnormal cell growth and tumorigenesis. Although the regulation of the Ras-ERK/MAPK signaling pathway by post-translational modification has been well elucidated, post-transcriptional regulations of this pathway are beginning to emerge in invertebrates and this work is extended to humans. In this review, we describe the conserved regulation of Ras-ERK/MAPK signaling by RNA-binding proteins (PUF, KH-domain, HuR, and LARP) and microRNAs (let-7 family miRNAs) and important implications for human diseases including cancers.
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PMID:Post-transcriptional regulation of the Ras-ERK/MAPK signaling pathway. 2168 67