title: Functional domains of the human androgen receptor.
abstract: A series of human androgen receptor (AR) deletion mutants was constructed to study the relationship between various structural domains and their different functions in the AR protein. Immunoblots of wild type AR and AR mutants expressed in COS-1 cells, revealed a doublet appearance of all AR proteins. One exception was an AR mutant lacking amino acid residues 51-211 that migrated as a single protein band, possibly due to altered post-translational modification. The steroid binding domain was found to be encoded by approx. 250 amino acid residues in the C-terminal end. Deletions and truncations in this part of the receptor abolished hormone binding. The N-terminal domain was observed to be essential for transcriptional activation. AR mutants lacking large parts of this domain were transcriptionally inactive. Deletion of the hormone binding domain yielded a constitutively active AR protein, indicating that in the absence of hormone this domain displays an inhibitory function. In the absence of ligand the wild type AR expressed in COS-1 cells was distributed over nucleus and cytoplasm. The addition of hormone directed all androgen receptors to the nucleus. In contrast, an AR mutant lacking part of the DNA binding domain and part of the hinge region, was almost exclusively cytoplasmic in the absence of hormone. This mutant lacks a conserved region, homologous to the SV40 large T- and nucleoplasmin nuclear localization signal. Hormone induced transfer of this AR mutant to the nucleus, indicating the presence of a second, hormone dependent nuclear targeting mechanism.
authors.affiliation: Department of Endocrinology and Reproduction, Erasmus University Rotterdam, The Netherlands.
authors.forename: G
authors.initials: G
authors.lastname: Jenster
authors.forename: J A
authors.initials: JA
authors.lastname: van der Korput
authors.forename: J
authors.initials: J
authors.lastname: Trapman
authors.forename: A O
authors.initials: AO
authors.lastname: Brinkmann
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D002460:Cell Line; D002872:Chromosome Deletion; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D008969:Molecular Sequence Data; D011944:Receptors, Androgen / Q000235:genetics / Q000378:metabolism*; D012689:Sequence Homology, Nucleic Acid; D013347:Subcellular Fractions; D014158:Transcription, Genetic; D014162:Transfection
chemical_list: D004268:DNA-Binding Proteins; D011944:Receptors, Androgen