Phosphorylation of Tudor-SN, a novel substrate of JNK, is involved in the efficient recruitment of Tudor-SN into stress granules

Biochim Biophys Acta Mol Cell Res. 2017 Mar;1864(3):562-571. doi: 10.1016/j.bbamcr.2016.12.018. Epub 2016 Dec 21.

Abstract

Posttranslational modifications of certain stress granule (SG) proteins are closely related to the assembly of SGs, a type of cytoplasmic foci structure. Our previous studies revealed that the Tudor staphylococcal nuclease (Tudor-SN) protein participates in the formation of SGs. However, the functional significance of potential Tudor-SN modifications during stress has not been reported. In this study, we demonstrated that the Tudor-SN protein was phosphorylated at threonine 103 (T103) upon stimulation with arsenite. In addition, c-Jun N-terminal kinase (JNK) was found to be responsible for Tudor-SN phosphorylation at the T103 site. We further illustrated that either a T103A mutation or the suppression of phosphorylation of T103 by the JNK inhibitor SP600125 inhibited the efficient recruitment of Tudor-SN into SGs. In addition, the T103A mutation could affect the physical binding of Tudor-SN with the G3BP (Ras-GAP SH3 domain-binding protein) protein but not with the HuR (Hu antigen R) protein and AGTR1-3'UTR (3'-untranslated region of angiotensin II receptor, type 1) mRNA cargo. These data suggested that JNK-enhanced Tudor-SN phosphorylation promotes the interaction between Tudor-SN and G3BP and facilitates the efficient recruitment of Tudor-SN into SGs under conditions of sodium arsenite-induced oxidative stress. This finding provides novel insights into the physiological function of Tudor-SN modification.

Keywords: C-Jun N-terminal kinase; Phosphorylation; Stress; Stress granules; Tudor-SN.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anthracenes / pharmacology
  • Arsenites / pharmacology
  • Carrier Proteins / genetics*
  • Carrier Proteins / metabolism
  • Cytoplasmic Granules / drug effects
  • Cytoplasmic Granules / metabolism*
  • Cytoplasmic Granules / ultrastructure
  • DNA Helicases
  • ELAV-Like Protein 1 / genetics
  • ELAV-Like Protein 1 / metabolism
  • Endonucleases
  • HeLa Cells
  • Humans
  • JNK Mitogen-Activated Protein Kinases / antagonists & inhibitors
  • JNK Mitogen-Activated Protein Kinases / genetics*
  • JNK Mitogen-Activated Protein Kinases / metabolism
  • Mutation
  • Nuclear Proteins / genetics*
  • Nuclear Proteins / metabolism
  • Oxidative Stress
  • Phosphorylation / drug effects
  • Poly-ADP-Ribose Binding Proteins
  • Protein Binding
  • Protein Kinase Inhibitors / pharmacology
  • Protein Processing, Post-Translational*
  • RNA Helicases
  • RNA Recognition Motif Proteins
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Receptor, Angiotensin, Type 1 / genetics
  • Receptor, Angiotensin, Type 1 / metabolism
  • Sodium Compounds / pharmacology
  • Threonine / metabolism

Substances

  • AGTR1 protein, human
  • Anthracenes
  • Arsenites
  • Carrier Proteins
  • ELAV-Like Protein 1
  • ELAVL1 protein, human
  • Nuclear Proteins
  • Poly-ADP-Ribose Binding Proteins
  • Protein Kinase Inhibitors
  • RNA Recognition Motif Proteins
  • RNA, Messenger
  • Receptor, Angiotensin, Type 1
  • Sodium Compounds
  • pyrazolanthrone
  • Threonine
  • sodium arsenite
  • JNK Mitogen-Activated Protein Kinases
  • Endonucleases
  • SND1 protein, human
  • DNA Helicases
  • G3BP1 protein, human
  • RNA Helicases