Phosphorylation adjacent to the nuclear localization signal of human dUTPase abolishes nuclear import: Structural and mechanistic insights

Rona, G., Marfori, M., Borsos, M., Scheer, I., Takacs, E., Toth, J., Babos, F., Magyar, A., Erdei, A., Bozoky, Z., Buday, L., Kobe, B. and Vertessy, B.G. (2013) Phosphorylation adjacent to the nuclear localization signal of human dUTPase abolishes nuclear import: Structural and mechanistic insights. Acta Crystallographica Section D: Biological Crystallography, 69 12: 2495-2505. doi:10.1107/S0907444913023354

Attached Files (Some files may be inaccessible until you login with your UQ eSpace credentials)
Name Description MIMEType Size Downloads
UQ320197_OA.pdf Full text (open access) application/pdf 1.44MB 0
UQ320197_Supp.pdf Supplementary data application/pdf 3.27MB 10

Author Rona, G.
Marfori, M.
Borsos, M.
Scheer, I.
Takacs, E.
Toth, J.
Babos, F.
Magyar, A.
Erdei, A.
Bozoky, Z.
Buday, L.
Kobe, B.
Vertessy, B.G.
Title Phosphorylation adjacent to the nuclear localization signal of human dUTPase abolishes nuclear import: Structural and mechanistic insights
Journal name Acta Crystallographica Section D: Biological Crystallography   Check publisher's open access policy
ISSN 0907-4449
1399-0047
Publication date 2013-12
Year available 2013
Sub-type Article (original research)
DOI 10.1107/S0907444913023354
Open Access Status File (Publisher version)
Volume 69
Issue 12
Start page 2495
End page 2505
Total pages 11
Place of publication Malden, United States
Publisher Wiley-Blackwell Publishing
Collection year 2014
Language eng
Subject 1315 Structural Biology
Formatted abstract
Phosphorylation adjacent to nuclear localization signals (NLSs) is involved in the regulation of nucleocytoplasmic transport. The nuclear isoform of human dUTPase, an enzyme that is essential for genomic integrity, has been shown to be phosphorylated on a serine residue (Ser11) in the vicinity of its nuclear localization signal; however, the effect of this phosphorylation is not yet known. To investigate this issue, an integrated set of structural, molecular and cell biological methods were employed. It is shown that NLS-adjacent phosphorylation of dUTPase occurs during the M phase of the cell cycle. Comparison of the cellular distribution of wild-type dUTPase with those of hyperphosphorylation- and hypophosphorylation-mimicking mutants suggests that phosphorylation at Ser11 leads to the exclusion of dUTPase from the nucleus. Isothermal titration microcalorimetry and additional independent biophysical techniques show that the interaction between dUTPase and importin-α, the karyopherin molecule responsible for 'classical' NLS binding, is weakened significantly in the case of the S11E hyperphosphorylation-mimicking mutant. The structures of the importin-α-wild-type and the importin-α- hyperphosphorylation-mimicking dUTPase NLS complexes provide structural insights into the molecular details of this regulation. The data indicate that the post-translational modification of dUTPase during the cell cycle may modulate the nuclear availability of this enzyme.
Keyword DUTPase
Importin
Nuclear import
Nuclear localization signal
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2014 Collection
School of Chemistry and Molecular Biosciences
 
Versions
Version Filter Type
Citation counts: TR Web of Science Citation Count  Cited 12 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 14 times in Scopus Article | Citations
Google Scholar Search Google Scholar
Created: Tue, 31 Dec 2013, 00:49:13 EST by System User on behalf of School of Chemistry & Molecular Biosciences