CK2 and GSK3 phosphorylation on S29 controls wild-type ATXN3 nuclear uptake

V. Pastori, E. Sangalli, P. Coccetti, C. Pozzi, S. Nonnis, G. Tedeschi, P. Fusi

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

In the present work we show that murine ATXN3 (ATXN3Q6) nuclear uptake is promoted by phosphorylation on serine 29, a highly conserved residue inside the Josephin domain. Both casein kinase 2 (CK2) and glycogen synthase kinase 3 (GSK3) are able to carry out phosphorylation on this residue. S29 phosphorylation was initially assessed in vitro on purified ATXN3Q6, and subsequently confirmed in transfected COS-7 cells, by MS analysis. Site-directed mutagenesis of S29 to an alanine was shown to strongly reduce nuclear uptake, in COS-7 transiently transfected cells overexpressing ATXN3Q6, while substitution with phospho-mimic aspartic acid restored the wild-type phenotype. Finally, treatment with CK2 and GSK3 inhibitors prevented S29 phosphorylation and strongly inhibited nuclear uptake, showing that both kinases are involved in ATXN3Q6 subcellular sorting. Although other authors have previously addressed this issue, we show for the first time that ATXN3 is phosphorylated inside the Josephin domain and that S29 phosphorylation is involved in nuclear uptake of ATXN3.

Original languageEnglish
Pages (from-to)583-592
Number of pages10
JournalBiochimica et Biophysica Acta - Molecular Basis of Disease
Volume1802
Issue number7-8
DOIs
Publication statusPublished - Jul 2010

Fingerprint

Glycogen Synthase Kinase 3
Casein Kinase II
Phosphorylation
COS Cells
Site-Directed Mutagenesis
Aspartic Acid
Alanine
Serine
Phosphotransferases
Phenotype

Keywords

  • ATXN3
  • CK2
  • GSK3
  • Mass spectrometry
  • Phosphorylation
  • Subcellular localization

ASJC Scopus subject areas

  • Molecular Biology
  • Molecular Medicine

Cite this

CK2 and GSK3 phosphorylation on S29 controls wild-type ATXN3 nuclear uptake. / Pastori, V.; Sangalli, E.; Coccetti, P.; Pozzi, C.; Nonnis, S.; Tedeschi, G.; Fusi, P.

In: Biochimica et Biophysica Acta - Molecular Basis of Disease, Vol. 1802, No. 7-8, 07.2010, p. 583-592.

Research output: Contribution to journalArticle

Pastori, V. ; Sangalli, E. ; Coccetti, P. ; Pozzi, C. ; Nonnis, S. ; Tedeschi, G. ; Fusi, P. / CK2 and GSK3 phosphorylation on S29 controls wild-type ATXN3 nuclear uptake. In: Biochimica et Biophysica Acta - Molecular Basis of Disease. 2010 ; Vol. 1802, No. 7-8. pp. 583-592.
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AU - Tedeschi, G.

AU - Fusi, P.

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