p34cdc2-mediated phosphorylation at T124 inhibits nuclear import of SV-40 T antigen proteins

Jans, D. A., Ackermann, M. J., Bischoff, J. R., Beach, D. H., Peters, R. (December 1991) p34cdc2-mediated phosphorylation at T124 inhibits nuclear import of SV-40 T antigen proteins. Journal of Cell Biology, 115 (5). pp. 1203-1212. ISSN 0021-9525

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URL: http://www.ncbi.nlm.nih.gov/pubmed/1659575
DOI: 10.1083/jcb.115.5.1203

Abstract

The nuclear import of transcription regulatory proteins appears to be used by the cell to trigger transitions in cell cycle, morphogenesis, and transformation. We have previously observed that the rate at which SV-40 T antigen fusion proteins containing a functional nuclear localization sequence (NLS; residues 126-132) are imported into the nucleus is enhanced in the presence of the casein kinase II (CK-II) site S111/112. In this study purified p34cdc2 kinase was used to phosphorylate T antigen proteins specifically at T124 and kinetic measurements at the single-cell level performed to assess its effect on nuclear protein import. T124 phosphorylation, which could be functionally simulated by a T-to-D124 substitution, was found to reduce the maximal extent of nuclear accumulation whilst negligibly affecting the import rate. The inhibition of nuclear import depended on the stoichiometry of phosphorylation. T124 and S111/112 could be phosphorylated independently of one another. Two alterative mechanisms were considered to explain the inhibition of nuclear import by T124 phosphorylation: inactivation of the NLS and cytoplasmic retention, respectively. Furthermore, we speculate that in vivo T124 phosphorylation may regulate the small but functionally significant amount of cytoplasmic SV-40 T antigen. A sequence comparison showed that many transcription regulatory proteins contain domains comprising potential CK-II-sites, cdc2-sites, and NLS. This raises the possibility that the three elements represent a functional unit regulating nuclear protein import.

Item Type: Paper
Uncontrolled Keywords: nf-kappa-b large tumor-antigen cell-cycle control sv40 large-t pore complex cdc2 kinase differential phosphorylation fluorescence microphotolysis catalytic subunit location signal
Subjects: bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > Cyclins
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > cdc2
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein expression > phosphorylation
organism description > virus
CSHL Authors:
Communities: CSHL labs > Beach lab
Depositing User: Matt Covey
Date: December 1991
Date Deposited: 21 Dec 2015 16:03
Last Modified: 21 Dec 2015 16:03
PMCID: PMC2289236
Related URLs:
URI: http://repository.cshl.edu/id/eprint/32119

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