6eih
From Proteopedia
The crystal structure of 14-3-3 epsilon in complex with the phosphorylated NELFE peptide
Structural highlights
Disease[1433E_HUMAN] Distal 17p13.3 microdeletion syndrome;17p13.3 microduplication syndrome;Miller-Dieker syndrome. Function[1433E_HUMAN] Adapter protein implicated in the regulation of a large spectrum of both general and specialized signaling pathways. Binds to a large number of partners, usually by recognition of a phosphoserine or phosphothreonine motif. Binding generally results in the modulation of the activity of the binding partner. Publication Abstract from PubMedUltraviolet (UV) light radiation induces the formation of bulky photoproducts in the DNA that globally affect transcription and splicing. However, the signaling pathways and mechanisms that link UV-light-induced DNA damage to changes in RNA metabolism remain poorly understood. Here we employ quantitative phosphoproteomics and protein kinase inhibition to provide a systems view on protein phosphorylation patterns induced by UV light and uncover the dependencies of phosphorylation events on the canonical DNA damage signaling by ATM/ATR and the p38 MAP kinase pathway. We identify RNA-binding proteins as primary substrates and 14-3-3 as direct readers of p38-MK2-dependent phosphorylation induced by UV light. Mechanistically, we show that MK2 phosphorylates the RNA-binding subunit of the NELF complex NELFE on Serine 115. NELFE phosphorylation promotes the recruitment of 14-3-3 and rapid dissociation of the NELF complex from chromatin, which is accompanied by RNA polymerase II elongation. p38-MK2 signaling axis regulates RNA metabolism after UV-light-induced DNA damage.,Borisova ME, Voigt A, Tollenaere MAX, Sahu SK, Juretschke T, Kreim N, Mailand N, Choudhary C, Bekker-Jensen S, Akutsu M, Wagner SA, Beli P Nat Commun. 2018 Mar 9;9(1):1017. doi: 10.1038/s41467-018-03417-3. PMID:29523821[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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Categories: Human | Large Structures | Akutsu, M | Beli, P | Wagner, S A | 14-3-3 | Nelf | Protein binding