| Autor: |
Z X, Zhou, M, Sar, J A, Simental, M V, Lane, E M, Wilson |
| Rok vydání: |
1994 |
| Předmět: |
|
| Zdroj: |
The Journal of biological chemistry. 269(18) |
| ISSN: |
0021-9258 |
| Popis: |
The amino acid sequence requirements for androgen-dependent androgen receptor nuclear import were determined by immunostaining transiently expressed full-length wild type and mutant human androgen receptors (AR) in monkey kidney COS cells and measuring transcriptional activity by cotransfection with a luciferase reporter vector in monkey kidney CV1 cells. Mutagenesis studies revealed a bipartite nuclear targeting sequence in the DNA binding and hinge regions at amino acids 617-633, consisting of two clusters of basic amino acids separated by 10 amino acids, (sequence: see text). In a series of deletion mutants, AR NH2-terminal fragments (residues 1-639 through 1-723) displayed constitutive nuclear import, and transcriptional activity was similar to that of the ligand-activated full-length wild type AR. In contrast, nuclear import and transcriptional activation were inhibited by sequence extensions into the steroid-binding domain (1-771). Constitutive nuclear import was regained in part by NH2-terminal deletions of full-length AR. Expression of AR/pyruvate kinase chimeras defined a sequence required for pre-dominant nuclear localization as residues 580-661, comprised of the second zinc finger region of the DNA-binding domain, the 17-amino-acid putative targeting sequence, and 28 residues of flanking carboxyl-terminal sequence. These studies suggest that the bipartite nuclear targeting sequence of AR includes flanking sequence and is modulated by interactions between the NH2-and carboxyl-terminal regions. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
|
