The androgen receptor (AR) is a steroid-activated transcription factor that is essential in male development and reproduction and in the progression of prostate cancer. Spinobulbar muscular atrophy (SBMA) is caused by a glutamine expansion in the N-terminal region of AR and causes selective degeneration of motor neurons in the spinal cord and brainstem in male patients. Recently, our laboratory has observed that AR specifically associates with actin and that the actin-binding protein, profilin, regulates polyglutamine aggregation, a pathologic hallmark of polyglutamine disease. These data, in combination with previous literature revealing actin-binding proteins as coregulators of AR, strongly implicate actin and actin-binding proteins in the regulation of AR. These findings may lead to a new understanding of steroid receptor regulation and the pathogenesis of SBMA. However, little is known about the nature of the AR/actin interaction. Thus, I propose to characterize the interaction between AR and actin by defining the region of AR required to associate with actin and identifying key regulators involved in the AR/actin interaction.
| Angeli, Suzanne; Shao, Jieya; Diamond, Marc I (2010) F-actin binding regions on the androgen receptor and huntingtin increase aggregation and alter aggregate characteristics. PLoS One 5:e9053 |
