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The identification of a functional nuclear localization signal in the Huntington disease protein.
- Source :
-
Brain research. Molecular brain research [Brain Res Mol Brain Res] 1995 Oct; Vol. 33 (1), pp. 165-73. - Publication Year :
- 1995
-
Abstract
- Positional cloning has shown that the Huntington disease (HD) mutation is an expanded trinucleotide repeat in the IT15 gene. Although this mutation clearly produces the HD phenotype, the function of the Huntington disease protein remains undefined. One recent immunocytochemical study suggested that the IT15 protein preferentially localizes to the nucleus of affected neuronal cells. If this result is accurate, it could link the biochemical function of this protein to nuclear activities such as gene regulation. To examine the nuclear transport of the Huntington disease protein, we searched for basic peptide motifs that could produce nuclear localization. One peptide (RRKGKEK) was identified that is highly homologous to a consensus nuclear localization signal. When fused to the cytoplasmic reporter protein, beta-galactosidase, nuclear localization was observed in stably transformed human cell lines. In a complementary study, an anti-peptide polyclonal antibody, raised against a sequence adjacent to the putative nuclear localization sequence, detected the IT15 protein in the nucleus of human cells. These results extend and confirm the previous localization studies and identify an IT15 peptide motif that can function for nuclear localization.
- Subjects :
- Amino Acid Sequence
Base Sequence
Biological Transport
Blotting, Western
Cell Line
Humans
Huntingtin Protein
Microscopy, Fluorescence
Molecular Sequence Data
Nerve Tissue Proteins
Huntington Disease metabolism
Nuclear Proteins analysis
Protein Structure, Tertiary
Proteins analysis
Signal Transduction physiology
Subjects
Details
- Language :
- English
- ISSN :
- 0169-328X
- Volume :
- 33
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Brain research. Molecular brain research
- Publication Type :
- Academic Journal
- Accession number :
- 8774958
- Full Text :
- https://doi.org/10.1016/0169-328x(95)00124-b