Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
Analysis of a developmentally regulated nuclear localization signal in Xenopus.
Standiford DM
,
Richter JD
.
???displayArticle.abstract???
The 289 residue nuclear oncoprotein encoded by the adenovirus 5 Ela gene contains two peptide sequences that behave as nuclear localization signals (NLS). One signal, located at the carboxy terminus, is like many other known NLSs in that it consists of a short stretch of basic residues (KRPRP) and is constitutively active in cells. The second signal resides within an internal 45 residue region of E1a that contains few basic residues or sequences that resemble other known NLSs. Moreover, this internal signal functions in injected Xenopus oocytes, but not in transfected Xenopus A6 cells, suggesting that it could be regulated developmentally (Slavicek et al. 1989. J. Virol. 63:4047). In this study, we show that the activity of this signal is sensitive to ATP depletion in vivo, efficiently directs the import of a 50 kD fusion protein and can compete with the E1a carboxy-terminal NLS for nuclear import. In addition, we have delineated the precise amino acid residues that comprise the second E1a NLS, and have assessed its utilization during Xenopus embryogenesis. Using amino acid deletion and substitution analyses, we show that the signal consists of the sequence FV(X)7-20MXSLXYM(X)4MF. By expressing in Xenopus embryos a truncated E1a protein that contains only the second NLS and by monitoring its cytoplasmic/nuclear distribution during development with indirect immunofluorescence, we find that the second NLS is utilized up to the early neurula stage. In addition, there appears to be a hierarchy among the embryonic germ layers as to when the second NLS becomes nonfunctional. For this reason, we refer to this NLS as the developmentally regulated nuclear localization signal (drNLS). The implications of these findings for early development are discussed.
Adam,
Cytosolic proteins that specifically bind nuclear location signals are receptors for nuclear import.
1991, Pubmed
Adam,
Cytosolic proteins that specifically bind nuclear location signals are receptors for nuclear import.
1991,
Pubmed
Akey,
Protein import through the nuclear pore complex is a multistep process.
1989,
Pubmed
,
Xenbase
Booher,
The fission yeast cdc2/cdc13/suc1 protein kinase: regulation of catalytic activity and nuclear localization.
1989,
Pubmed
Breeuwer,
Facilitated nuclear transport of histone H1 and other small nucleophilic proteins.
1990,
Pubmed
Culp,
The 289-amino acid E1A protein of adenovirus binds zinc in a region that is important for trans-activation.
1988,
Pubmed
Danielsen,
The mouse glucocorticoid receptor: mapping of functional domains by cloning, sequencing and expression of wild-type and mutant receptor proteins.
1986,
Pubmed
Devereux,
A comprehensive set of sequence analysis programs for the VAX.
1984,
Pubmed
Dreyer,
Differential accumulation of oocyte nuclear proteins by embryonic nuclei of Xenopus.
1987,
Pubmed
,
Xenbase
Dreyer,
Fate and nuclear localization of germinal vesicle proteins during embryogenesis.
1989,
Pubmed
,
Xenbase
Dumont,
Oogenesis in Xenopus laevis (Daudin). I. Stages of oocyte development in laboratory maintained animals.
1972,
Pubmed
,
Xenbase
Dworetzky,
The effects of variations in the number and sequence of targeting signals on nuclear uptake.
1988,
Pubmed
,
Xenbase
Feldherr,
Movement of a karyophilic protein through the nuclear pores of oocytes.
1984,
Pubmed
,
Xenbase
Fischer,
Diversity in the signals required for nuclear accumulation of U snRNPs and variety in the pathways of nuclear transport.
1991,
Pubmed
,
Xenbase
Gao,
Distal protein sequences can affect the function of a nuclear localization signal.
1992,
Pubmed
Garcia-Bustos,
Nuclear protein localization.
1991,
Pubmed
Goldfarb,
Synthetic peptides as nuclear localization signals.
,
Pubmed
,
Xenbase
Hollenberg,
Primary structure and expression of a functional human glucocorticoid receptor cDNA.
1985,
Pubmed
Hunt,
Cytoplasmic anchoring proteins and the control of nuclear localization.
1989,
Pubmed
James,
Deletion of the regulatory domain of protein kinase C alpha exposes regions in the hinge and catalytic domains that mediate nuclear targeting.
1992,
Pubmed
Jelsma,
Sequences in E1A proteins of human adenovirus 5 required for cell transformation, repression of a transcriptional enhancer, and induction of proliferating cell nuclear antigen.
1989,
Pubmed
Kalderon,
A short amino acid sequence able to specify nuclear location.
1984,
Pubmed
Leptin,
Cell shape changes during gastrulation in Drosophila.
1990,
Pubmed
Lyons,
Pentapeptide nuclear localization signal in adenovirus E1a.
1987,
Pubmed
Michaud,
Microinjected U snRNAs are imported to oocyte nuclei via the nuclear pore complex by three distinguishable targeting pathways.
1992,
Pubmed
,
Xenbase
Michaud,
Multiple pathways in nuclear transport: the import of U2 snRNP occurs by a novel kinetic pathway.
1991,
Pubmed
,
Xenbase
Miesfeld,
Genetic complementation of a glucocorticoid receptor deficiency by expression of cloned receptor cDNA.
1986,
Pubmed
Miller,
The nuclear-cytoplasmic distribution of the Xenopus nuclear factor, xnf7, coincides with its state of phosphorylation during early development.
1991,
Pubmed
,
Xenbase
Moll,
The role of phosphorylation and the CDC28 protein kinase in cell cycle-regulated nuclear import of the S. cerevisiae transcription factor SWI5.
1991,
Pubmed
Muller,
The glucocorticoid receptor.
1991,
Pubmed
Nelson,
Context affects nuclear protein localization in Saccharomyces cerevisiae.
1989,
Pubmed
Newmeyer,
In vitro transport of a fluorescent nuclear protein and exclusion of non-nuclear proteins.
1986,
Pubmed
,
Xenbase
Newmeyer,
Nuclear import can be separated into distinct steps in vitro: nuclear pore binding and translocation.
1988,
Pubmed
,
Xenbase
Newmeyer,
Assembly in vitro of nuclei active in nuclear protein transport: ATP is required for nucleoplasmin accumulation.
1986,
Pubmed
,
Xenbase
Paine,
Nucleocytoplasmic exchange of macromolecules.
1972,
Pubmed
Picard,
Two signals mediate hormone-dependent nuclear localization of the glucocorticoid receptor.
1987,
Pubmed
Pines,
Human cyclins A and B1 are differentially located in the cell and undergo cell cycle-dependent nuclear transport.
1991,
Pubmed
Richardson,
Nuclear protein migration involves two steps: rapid binding at the nuclear envelope followed by slower translocation through nuclear pores.
1988,
Pubmed
,
Xenbase
Richter,
Heterogeneity of adenovirus type 5 E1A proteins: multiple serine phosphorylations induce slow-migrating electrophoretic variants but do not affect E1A-induced transcriptional activation or transformation.
1988,
Pubmed
Richter,
A first exon-encoded domain of E1A sufficient for posttranslational modification, nuclear-localization, and induction of adenovirus E3 promoter expression in Xenopus oocytes.
1985,
Pubmed
,
Xenbase
Rihs,
The rate of nuclear cytoplasmic protein transport is determined by the casein kinase II site flanking the nuclear localization sequence of the SV40 T-antigen.
1991,
Pubmed
Rihs,
Nuclear transport kinetics depend on phosphorylation-site-containing sequences flanking the karyophilic signal of the Simian virus 40 T-antigen.
1989,
Pubmed
Robbins,
Two interdependent basic domains in nucleoplasmin nuclear targeting sequence: identification of a class of bipartite nuclear targeting sequence.
1991,
Pubmed
,
Xenbase
Roth,
A gradient of nuclear localization of the dorsal protein determines dorsoventral pattern in the Drosophila embryo.
1989,
Pubmed
Roux,
Nuclear localization of c-Fos, but not v-Fos proteins, is controlled by extracellular signals.
1990,
Pubmed
Rushlow,
The graded distribution of the dorsal morphogen is initiated by selective nuclear transport in Drosophila.
1989,
Pubmed
Sanger,
DNA sequencing with chain-terminating inhibitors.
1977,
Pubmed
Schmitz,
Proteins controlling the nuclear uptake of NF-kappa B, Rel and dorsal.
1991,
Pubmed
Schneider,
Mutational analysis of the adenovirus E1a gene: the role of transcriptional regulation in transformation.
1987,
Pubmed
Shiurba,
Nuclear translocation of fibroblast growth factor during Xenopus mesoderm induction.
1991,
Pubmed
,
Xenbase
Simon,
The degradation sequence of adenovirus E1A consists of the amino-terminal tetrapeptide Met-Arg-His-Ile.
1990,
Pubmed
,
Xenbase
Slack,
Growth factors as inducing agents in early Xenopus development.
1990,
Pubmed
,
Xenbase
Slavicek,
A karyophilic signal sequence in adenovirus type 5 E1A is functional in Xenopus oocytes but not in somatic cells.
1989,
Pubmed
,
Xenbase
Steward,
Relocalization of the dorsal protein from the cytoplasm to the nucleus correlates with its function.
1989,
Pubmed
Stochaj,
A yeast protein that binds nuclear localization signals: purification localization, and antibody inhibition of binding activity.
1991,
Pubmed
Webster,
trans-dominant mutants of E1A provide genetic evidence that the zinc finger of the trans-activating domain binds a transcription factor.
1991,
Pubmed
Wedlich,
Cell specificity of nuclear protein antigens in the development of Xenopus species.
1988,
Pubmed
,
Xenbase
Yamasaki,
Identification of four nuclear transport signal-binding proteins that interact with diverse transport signals.
1989,
Pubmed
,
Xenbase
van Zee,
A hydrophobic protein sequence can override a nuclear localization signal independently of protein context.
1991,
Pubmed
