Proteomics,Multiomics

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MS-based identification of AcP10 interaction partners.


ABSTRACT: In times of cellular stress, such as during virus infections, the integrated stress response (ISR) blocks translation initiation through phosphorylation of the essential translation initiation factor eIF2. Phosphorylated eIF2 (p-eIF2) sequesters the eIF2-specific guanidine exchange factor (GEF) eIF2B, thereby preventing eIF2 recycling. Here we describe the first example of a viral ISR antagonist that inhibits the ISR at its most central step: the interplay between p-eIF2 and eIF2B. Using AP-MS, we determine that BW10 binds eIF2B. There, it selectively displaces eIF2B’s inhibitor p-eIF2 without affecting the association of its substrate eIF2. By this mechanism, BW10 renders cellular translation immune to regulation by eIF2 phosphorylation. Thus, under stress conditions BW10 creates the unprecedented situation of high levels of p-eIF2 coinciding with unimpaired translation.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Cell Culture

SUBMITTER: Piero Giansanti  

LAB HEAD: Albert J. R. Heck

PROVIDER: PXD011879 | Pride | 2020-07-24

REPOSITORIES: Pride

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