Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.2.1.23 (beta-galactosidase)
 14,648 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The composition and subcellular trafficking of subviral preintegration complexes are reported to vary among the different retroviruses. The process by which the avian sarcoma virus (ASV) preintegration complex gains access to target chromatin remains unknown. Here we report that ASV integrase (IN) expressed as a fusion to beta-galactosidase accumulates in the nuclei of transfected COS-1 cells. In contrast, human immunodeficiency type 1 (HIV-1) IN-beta-galactosidase fusions expressed similarly are predominantly cytoplasmic. To identify the region of ASV IN that specifies nuclear localization, various subdomains of the protein were expressed as beta-galactosidase fusions and their subcellular locations were assessed cytochemically and by indirect immunofluorescence. These analyses showed that the ASV IN protein possesses a functional nuclear localization signal that spans amino acids 206 to 235 and displays limited homology with known nuclear transport signals.
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PMID:Subcellular localization of avian sarcoma virus and human immunodeficiency virus type 1 integrases. 898 28

A sequence of 21 amino acids (aa) in the C-terminal region of the 286-aa avian sarcoma virus (ASV) integrase (IN) protein has been shown previously to mediate nuclear localization of both IN and beta-galactosidase (betaGal) protein fused to it. This karyophilic sequence includes a high proportion of prolines and residues with basic side chains. In this report, site-directed mutagenesis was used to introduce single aa substitutions of several of these residues. Indirect immunofluorescence showed that IN-betaGal fusion constructs with Ala substitutions for sequence constituents K206, P215, K225 or R227 had lost the exclusive nuclear localization capability of the wild-type fusion. A fusion protein with the conservative substitution K206R retained the nuclear localization capacity. The site-specific substitutions that reduced karyophilic activity had no effect on the processing or joining activities of IN in vitro. However, the introduction of three of the four Ala codon substitutions into viral DNA clones caused a significant delay in viral replication following transfection of cycling chicken embryo fibroblasts. These results are consistent with a possible role for ASV IN in nuclear targeting.
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PMID:Characterization of the nuclear localization signal in the avian sarcoma virus integrase. 985 17