Androgen receptor regulates nuclear trafficking and nuclear domain residency of corepressor HDAC7 in a ligand-dependent fashion

作者：Karvonen Ulla; Janne Olli A; Palvimo Jorma J^*

来源：Experimental Cell Research, 2006, 312(16): 3165-3183.

DOI：10.1016/j.yexcr.2006.06.018

• androgen receptor
• androgen
• antiandrogen
• histone deacetylase (HDAC) 7
• nuclear domain
• nuclear trafficking
• nuclear speckle
• PML
• SUMO

In addition to chromosomal proteins, histone deacetylases (HDACs) target transcription factors in transcriptional repression. Here, we show that the class II HDAC family member HDAC7 is an efficient corepressor of the androgen receptor (AR). HDAC7 resided in the cytoplasm in the absence of AR or a cognate ligand, but hormone-occupancy of AR induced nuclear transfer of HDAC7 Nuclear colocalization pattern of AR and HDAC7 was dependent on the nature of the ligand. In the presence of testosterone, a portion of HDAC7 localized to pearl-like nuclear domains, whereas AR occupied with antagonistic ligands cyproterone acetate- or casodex (bicalutamide) recruited HDAC7 from these domains to colocalize with the receptor in speckles and nucleoplasm in a more complete fashion. Ectopic expression of PML-3 relieved the repressive effect of HDAC7 on AR function by sequestering HDAC7 to PML-3 domains. AR acetylation at Lys630/632/633 was not the target of HDAC7 repression, since repression of AR function was independent of these acetylation sites. Moreover, the deacetylase activity of HDAC7 was in part dispensable in the repression of AR function. In sum, our results identify HDAC7 as a novel AR corepressor whose subcellular and subnuclear compartmentalization can be regulated in an androgen-selective manner.

• 出版日期2006-10-1