Distal protein sequences can affect the function of a nuclear localization signal
- PMID: 1545814
- PMCID: PMC369566
- DOI: 10.1128/mcb.12.3.1330-1339.1992
Distal protein sequences can affect the function of a nuclear localization signal
Abstract
The major DNA-binding protein, or infected-cell protein 8 (ICP8), encoded by herpes simplex virus can localize to the cell nucleus independently of other viral proteins. To define the nuclear localization signals within ICP8, we performed several forms of mutagenesis on the cloned ICP8 gene. Deletion analysis of the ICP8 gene showed that several portions of ICP8 are involved in its nuclear localization. To determine whether these regions were independent localization signals, we introduced various portions of the ICP8 gene into a series of cassette plasmids which allowed expression of fusion proteins containing pyruvate kinase, normally a cytoplasmic protein, fused to various portions of ICP8. These results showed that the carboxyl-terminal 28 residues are the only portion of ICP8 capable of targeting protein kinase into the nucleus. However, inclusion of certain additional regions of ICP8 into the fusion protein led to an inhibition of nuclear localization. Therefore, the carboxyl-terminal 28 residues of ICP8 can act independently as a nuclear localization signal, but certain conformational constraints or folding or assembly requirements in the remainder of the protein can affect the nuclear localization of the protein. Our results demonstrate that sequences distant from a nuclear localization signal can affect its ability to function. A set of fusion vectors has been isolated which should be of general use for making 5' or 3' fusions in any reading frame to rapidly map localization signals.
Similar articles
-
Intragenic complementation of herpes simplex virus ICP8 DNA-binding protein mutants.J Virol. 1993 Feb;67(2):876-85. doi: 10.1128/JVI.67.2.876-885.1993. J Virol. 1993. PMID: 8380469 Free PMC article.
-
Genetic evidence for multiple nuclear functions of the herpes simplex virus ICP8 DNA-binding protein.J Virol. 1989 Dec;63(12):5258-67. doi: 10.1128/JVI.63.12.5258-5267.1989. J Virol. 1989. PMID: 2555553 Free PMC article.
-
Intracellular localization of the herpes simplex virus type-1 origin binding protein, UL9.Virology. 1996 Oct 15;224(2):380-9. doi: 10.1006/viro.1996.0545. Virology. 1996. PMID: 8874499
-
C-terminal region of herpes simplex virus ICP8 protein needed for intranuclear localization.Virology. 2003 May 10;309(2):219-31. doi: 10.1016/s0042-6822(03)00108-9. Virology. 2003. PMID: 12758170
-
Genetic identification of a portion of the herpes simplex virus ICP8 protein required for DNA-binding.Virology. 1988 Apr;163(2):319-29. doi: 10.1016/0042-6822(88)90272-3. Virology. 1988. PMID: 2833010
Cited by
-
The early UL31 gene of equine herpesvirus 1 encodes a single-stranded DNA-binding protein that has a nuclear localization signal sequence at the C-terminus.Virology. 2012 Oct 25;432(2):306-15. doi: 10.1016/j.virol.2012.05.031. Epub 2012 Jun 20. Virology. 2012. PMID: 22721961 Free PMC article.
-
Mutations in the beta-tubulin gene TUBB2B result in asymmetrical polymicrogyria.Nat Genet. 2009 Jun;41(6):746-52. doi: 10.1038/ng.380. Epub 2009 May 24. Nat Genet. 2009. PMID: 19465910 Free PMC article.
-
Overproduction of v-Myc in the nucleus and its excess over Max are not required for avian fibroblast transformation.Mol Cell Biol. 1993 Jun;13(6):3623-31. doi: 10.1128/mcb.13.6.3623-3631.1993. Mol Cell Biol. 1993. PMID: 8497274 Free PMC article.
-
Nuclear localization signals overlap DNA- or RNA-binding domains in nucleic acid-binding proteins.Nucleic Acids Res. 1995 May 25;23(10):1647-56. doi: 10.1093/nar/23.10.1647. Nucleic Acids Res. 1995. PMID: 7540284 Free PMC article. Review. No abstract available.
-
Nuclear and nucleolar targeting of human ribosomal protein S6.Mol Biol Cell. 1995 Dec;6(12):1875-85. doi: 10.1091/mbc.6.12.1875. Mol Biol Cell. 1995. PMID: 8590812 Free PMC article.
References
Publication types
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Full Text Sources
Other Literature Sources