Back to Search
Start Over
The monopartite nuclear localization signal of autoimmune regulator mediates its nuclear import and interaction with multiple importin alpha molecules
- Source :
- The FEBS journal. 273(2)
- Publication Year :
- 2006
-
Abstract
- Autoimmune regulator (AIRE) is a transcriptional regulator involved in establishing immunological self-tolerance. Mutations in the AIRE gene lead to the development of the autosomal, recessively inherited, organ-specific autoimmune disease, autoimmune polyendocrinopathy candidiasis ectodermal dystrophy (APECED). The AIRE protein is mainly localized in the cell nucleus where it is associated with nuclear bodies. The N-terminal part of AIRE has been previously shown to mediate nuclear localization of the protein. However, the functional nuclear localization signal (NLS) and nuclear import mechanisms of AIRE have not been identified. We show that, although the amino-acid sequence of AIRE contains a potential bipartite NLS consisting of amino acids 110-114 and 131-133, only the latter part constitutes a functional NLS. Furthermore, we show by in vitro binding assays that AIRE interacts with multiple members of the nuclear transport receptor importin alpha family, mainly alpha1, alpha3, and alpha5, and that these interactions depend on the intactness of the Arg-Lys-rich NLS of AIRE. In addition, we found that AIRE binds to the 'minor' NLS-binding site of importin alpha3 and alpha5 proteins consisting of the C-terminal armadillo repeats 7-9. Our findings strongly suggest that the nuclear import of AIRE is mediated by the classical importin alpha/beta pathway through binding to several importin alpha family members.
- Subjects :
- alpha Karyopherins
Molecular Sequence Data
Nuclear Localization Signals
Importin
Biology
environment and public health
Biochemistry
03 medical and health sciences
0302 clinical medicine
Two-Hybrid System Techniques
Chlorocebus aethiops
medicine
NLS
Animals
Amino Acid Sequence
Molecular Biology
030304 developmental biology
Genetics
Cell Nucleus
0303 health sciences
Microscopy, Confocal
Cell Biology
Autoimmune polyendocrinopathy
Autoimmune regulator
3. Good health
Cell biology
Cell nucleus
Protein Transport
medicine.anatomical_structure
030220 oncology & carcinogenesis
Armadillo repeats
COS Cells
Mutagenesis, Site-Directed
Nuclear transport
Nuclear localization sequence
Plasmids
Protein Binding
Transcription Factors
Subjects
Details
- ISSN :
- 1742464X
- Volume :
- 273
- Issue :
- 2
- Database :
- OpenAIRE
- Journal :
- The FEBS journal
- Accession number :
- edsair.doi.dedup.....e73152aebfcc3006a46deb24d0e7b77b