Reactome | SMG1 phosphorylates UPF1 (enhanced by Exon Junction Complex)

SMG1 phosphorylates UPF1 (enhanced by Exon Junction Complex)

Stable Identifier

R-HSA-927889

Type

Reaction [transition]

Species

Homo sapiens

Compartment

cytosol

ReviewStatus

5/5

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SMG1 phosphorylates UPF1 (enhanced by Exon Junction Complex)

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SMG1 phosphorylates UPF1 in vitro and in vivo (Denning et al. 2001, Yamashita et al. 2001, Kashima et al. 2006). Serines 1073, 1078, 1096, and 1116 in isoform 2 (Serines 1084, 1089, 1107, 1127 in isoform 1) are phosphorylated in vitro and phosphorylation at serines 1078 and 1096 has been confirmed in vivo (Yamashita et al. 2001, Ohnishi et al. 2003, Kashima et al. 2006). UPF1 also contains additional serine and threonine residues that could be phosphorylated. SMG8 and SMG9 associate with SMG1 and regulate the kinase activity of SMG1 (Yamashita et al. 2009). The phosphorylation reaction is rate-limiting in nonsense-mediated decay and is therefore regarded as a licensing step (reviewed in Rebbapragada and Lykke-Andersen 2009). Phosphorylation is enhanced by the exon junction complex, which can interact with UPF1 via UPF2 and/or UPF3 (Kashima et al. 2006, Ivanov et al. 2008) or via Y14:Magoh (Ivanov et al. 2008). SMG8 and SMG9 bind SMG1 and regulate its kinase activity (Yamashita et al. 2009, Fernandez et al. 2011).

Literature References

PubMed ID	Title	Journal	Year
19417104	SMG-8 and SMG-9, two novel subunits of the SMG-1 complex, regulate remodeling of the mRNA surveillance complex during nonsense-mediated mRNA decay Ohno, S, Katsuhata, Y, Yamashita, A, Ohnishi, T, Iwamatsu, A, Anderson, P, Izumi, N, Kurata, R, Hirano, H, Muramatsu, R, Morita, T, Saari, B, Hachiya, T, Kashima, I	Genes Dev	2009
11331269	Cloning of a novel phosphatidylinositol kinase-related kinase: characterization of the human SMG-1 RNA surveillance protein Jamieson, L, Thompson, EA, Maquat, LE, Denning, G, Fields, AP	J Biol Chem	2001
14636577	Phosphorylation of hUPF1 induces formation of mRNA surveillance complexes containing hSMG-5 and hSMG-7 Ohno, S, Grimson, A, Yamashita, A, Ohnishi, T, Anderson, P, Hachiya, T, Anders, KR, Hentze, MW, Schell, T, Kashima, I	Mol Cell	2003
11544179	Human SMG-1, a novel phosphatidylinositol 3-kinase-related protein kinase, associates with components of the mRNA surveillance complex and is involved in the regulation of nonsense-mediated mRNA decay Ohno, S, Taya, Y, Yamashita, A, Ohnishi, T, Kashima, I	Genes Dev	2001
20817927	Characterization of SMG-9, an essential component of the nonsense-mediated mRNA decay SMG1C complex Bartolomé, RA, Ohno, S, Bamba, Y, Llorca, O, Yamashita, A, Teixidó, J, Arias-Palomo, E, Fernández, IS, Canales, MA	Nucleic Acids Res	2011
16452507	Binding of a novel SMG-1-Upf1-eRF1-eRF3 complex (SURF) to the exon junction complex triggers Upf1 phosphorylation and nonsense-mediated mRNA decay Kataoka, N, Dreyfuss, G, Ohno, S, Hoshino, S, Morishita, R, Yamashita, A, Ohno, M, Izumi, N, Kashima, I	Genes Dev	2006
19359157	Execution of nonsense-mediated mRNA decay: what defines a substrate? Rebbapragada, I, Lykke-Andersen, J	Curr Opin Cell Biol	2009