Author:

Keywords:

androgen receptor, dna binding, nuclear, hinge region, intranuclear mobility, transcriptional activity, dna-binding domain, glucocorticoid-receptor, progesterone-receptor, response elements, prostate-cancer, nuclear import, in-vivo, alpha, transactivation, Science & Technology, Life Sciences & Biomedicine, Biochemistry & Molecular Biology, Cell Biology, Androgen receptor, DNA binding, Hinge region, Intranuclear mobility, Transcriptional activity, DNA-BINDING, TRANSCRIPTIONAL ACTIVITY, GLUCOCORTICOID-RECEPTOR, RESPONSE ELEMENT, PROSTATE-CANCER, NUCLEAR IMPORT, IN-VIVO, ALPHA, PROTEIN, ACETYLATION, Amino Acid Motifs, Amino Acid Substitution, Animals, Binding Sites, COS Cells, Cell Nucleus, Chlorocebus aethiops, DNA, Fluorescence Recovery After Photobleaching, HeLa Cells, Humans, Mutagenesis, Site-Directed, Protein Stability, Protein Structure, Tertiary, Receptors, Androgen, Recombinant Fusion Proteins, Sequence Deletion, Transcriptional Activation, Hela Cells, 0601 Biochemistry and Cell Biology, 0606 Physiology, 1103 Clinical Sciences, 3101 Biochemistry and cell biology, 3205 Medical biochemistry and metabolomics, 3211 Oncology and carcinogenesis

Abstract:

The androgen receptor protein has specific domains involved in DNA binding, ligand binding, and transactivation, whose activities need to be integrated during transcription activation. The hinge region, more particular a (RKLKK633)-R-629 motif, seems to play a crucial role in this process. Indeed, although the motif is not part of the DNA-binding domain, its positive residues are involved in optimal DNA binding and nuclear translocation as shown by mutation analysis. When the mutated ARs are forced into the nucleus, however, the residues seem to play different roles in transactivation. Moreover, we show by FRAP analysis that during activation, the AR is distributed in the nucleus in a mobile and two immobile fractions, and that mutations in the (RKLKK633)-R-629 motif affect the distribution of the AR over these three intranuclear fractions. Taken together, the (RKLKK633)-R-629 motif is a multifunctional motif that integrates nuclear localization, receptor stability, DNA binding, transactivation potential and intranuclear mobility.