Heat Shock-Induced Dephosphorylation of Eukaryotic Elongation Factor 1B?L by Protein Phosphatase 1.

ABSTRACT: Several variant proteins are produced from EEF1D, including two representative proteins produced via alternative splicing machinery. One protein is the canonical translation eukaryotic elongation factor eEF1B?1, and the other is the heat shock-responsive transcription factor eEF1B?L. eEF1B?1 is phosphorylated by cyclin-dependent kinase 1 (CDK1), but the machinery controlling eEF1B?L phosphorylation and dephosphorylation has not been clarified. In this study, we found that both proteins were dephosphorylated under heat shock and proteotoxic stress, and this dephosphorylation was inhibited by okadaic acid. Using proteins with mutations at putative phosphorylated residues, we revealed that eEF1B?1 and eEF1B?L are phosphorylated at S133 and S499, respectively, and these residues are both CDK1 phosphorylation sites. The eEF1B?L S499A mutant more strongly activated HSPA6 promoter-driven reporter than the wild-type protein and S499D mutant. Furthermore, protein phosphatase 1 (PP1) was co-immunoprecipitated with eEF1B?1 and eEF1B?L, and PP1 dephosphorylated both proteins in vitro. Thus, this study clarified the role of phosphorylation/dephosphorylation in the functional regulation of eEF1B?L during heat shock.

SUBMITTER: Kaitsuka T 

PROVIDER: S-EPMC7841112 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature