Androgen induces a switch from cytoplasmic retention to nuclear import of the androgen receptor.
Mol Cell Biol
; 33(24): 4766-78, 2013 Dec.
Article
en En
| MEDLINE
| ID: mdl-24100013
ABSTRACT
The androgen receptor (AR) has critical functions as a transcription factor in both normal and cancer cells, but the specific mechanisms that regulate its nuclear localization are not well defined. We found that an AR mutation commonly reported in prostate cancer generates an androgen-independent gain of function for nuclear import. The substitution, Thr877Ala, is within the ligand-binding domain, but the nuclear import gain of function is mediated by the bipartite nuclear localization signal (NLS) spanning the DNA-binding domain (DBD) and hinge region. Bipartite NLS activity depends on the structure provided by the DBD, and protein interactions with the bipartite NLS are repressed by the hinge region. The bipartite NLS is recognized by importin 7, a nuclear import receptor for several proteins. Importin 7 binding to AR, however, inhibits import by shielding the bipartite NLS. Androgen binding relieves the inhibition by inducing a switch that promotes exchange of importin 7 for karyopherin alpha import receptors. Importin 7 contributes to the regulation of AR import by restraining import until androgen is detected in the cytoplasm.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Receptores Androgénicos
/
Núcleo Celular
/
Receptores Citoplasmáticos y Nucleares
/
Sustitución de Aminoácidos
/
Carioferinas
/
Andrógenos
Tipo de estudio:
Prognostic_studies
Límite:
Animals
/
Humans
/
Male
Idioma:
En
Revista:
Mol Cell Biol
Año:
2013
Tipo del documento:
Article