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CK2 and GSK3 phosphorylation on S29 controls wild-type ATXN3 nuclear uptake.
- Source :
-
Biochimica et biophysica acta [Biochim Biophys Acta] 2010 Jul-Aug; Vol. 1802 (7-8), pp. 583-92. Date of Electronic Publication: 2010 Mar 27. - Publication Year :
- 2010
-
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.<br /> (Copyright 2010 Elsevier B.V. All rights reserved.)
- Subjects :
- Active Transport, Cell Nucleus genetics
Amino Acid Sequence
Animals
Ataxin-3
COS Cells
Casein Kinase II physiology
Cells, Cultured
Chlorocebus aethiops
Glycogen Synthase Kinase 3 physiology
Humans
Mice
Molecular Sequence Data
Mutant Proteins chemistry
Mutant Proteins genetics
Mutant Proteins metabolism
Nuclear Proteins chemistry
Nuclear Proteins genetics
Phosphorylation physiology
Sequence Homology, Amino Acid
Transcription Factors chemistry
Transcription Factors genetics
Casein Kinase II metabolism
Cell Nucleus metabolism
Glycogen Synthase Kinase 3 metabolism
Nuclear Proteins metabolism
Serine metabolism
Transcription Factors metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 0006-3002
- Volume :
- 1802
- Issue :
- 7-8
- Database :
- MEDLINE
- Journal :
- Biochimica et biophysica acta
- Publication Type :
- Academic Journal
- Accession number :
- 20347968
- Full Text :
- https://doi.org/10.1016/j.bbadis.2010.03.007