Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.1.3.16 (calcineurin)
 17,112 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

mRNAs that contain premature stop codons are degraded selectively and rapidly in eukaryotes, a phenomenon termed 'nonsense-mediated mRNA decay' (NMD). We report here molecular analysis of smg-5, which encodes a novel protein required for NMD in Caenorhabditis elegans. Using a combination of immunoprecipitation and yeast two-hybrid assays, we identified a series of protein-protein interactions involving SMG-5. SMG-5 interacts with at least four proteins: (i) SMG-7, a previously identified protein required for NMD; (ii) SMG-2, a phosphorylated protein required for NMD in worms, yeasts and mammals; (iii) PR65, the structural subunit of protein phosphatase 2A (PP2A); and (iv) PP2A(C), the catalytic subunit of PP2A. Previous work demonstrated that both SMG-5 and SMG-7 are required for efficient dephosphorylation of SMG-2. Our results suggest that PP2A is the SMG-2 phosphatase, and the role of SMG-5 is to direct PP2A to its SMG-2 substrate. We discuss cycles of SMG-2 phosphorylation and their roles in NMD.
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PMID:SMG-5, required for C.elegans nonsense-mediated mRNA decay, associates with SMG-2 and protein phosphatase 2A. 1255 64

Eukaryotic mRNAs containing premature termination codons (PTCs) are degraded by a process known as nonsense-mediated mRNA decay (NMD). NMD has been suggested to require the recognition of PTC by an mRNA surveillance complex containing UPF1/SMG-2. In multicellular organisms, UPF1/SMG-2 is a phosphoprotein, and its phosphorylation contributes to NMD. Here we show that phosphorylated hUPF1, the human ortholog of UPF1/SMG-2, forms a complex with human orthologs of the C. elegans NMD proteins SMG-5 and SMG-7. The complex also associates with protein phosphatase 2A (PP2A), resulting in dephosphorylation of hUPF1. Overexpression of hSMG-5 mutants that retain interaction with P-hUPF1 but which cannot induce its dephosphorylation impair NMD, suggesting that NMD requires P-hUPF1 dephosphorylation. We also show that P-hUPF1 forms distinct complexes containing different isoforms of hUPF3A. We propose that sequential phosphorylation and dephosphorylation of hUPF1 by hSMG-1 and PP2A, respectively, contribute to the remodeling of the mRNA surveillance complex.
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PMID:Phosphorylation of hUPF1 induces formation of mRNA surveillance complexes containing hSMG-5 and hSMG-7. 1463 63