ARA67/PAT1 functions as a repressor to suppress androgen receptor transactivation.
The androgen receptor (AR) may recruit multiple coregulators for proper or optimal transactivation. Here we report the identification and characterization of ARA67/PAT1 as an AR coregulator from a prostate cDNA library. ARA67/PAT1 was screened out as an AR N terminus interacting protein. Interaction mapping shows that the cooperation of multiple domains within ARA67/PAT1 may be required for the maximal interaction with AR. ARA67/PAT1 functions as a repressor with better suppressive effects on AR compared to glucocorticoid receptor and estrogen receptor. Further mechanism dissection reveals that the interrupted AR cytoplasmic-nuclear shuttling may play a major role in ARA67/PAT1 mediated suppression on AR. Together, these results suggest that ARA67/PAT1 may function as a novel repressor that can modulate AR function in prostate cancer.
Zhang
Yanqing
Y
Department of Pathology, Urology, and Radiation Oncology and Cancer Center, George Whipple Laboratory for Cancer Research, University of Rochester Medical Center, Rochester, New York 14642, USA.
Yang
Yue
Y
Yeh
Shuyuan
S
Chang
Chawnshang
C
D026905:Amino Acid Transport Systems / Q000378:metabolism*; D000818:Animals; D006801:Humans; D008024:Ligands; D008297:Male; D009928:Organ Specificity; D011944:Receptors, Androgen / Q000096:biosynthesis / Q000235:genetics*; D027981:Symporters; D015533:Transcriptional Activation; D020798:Two-Hybrid System Techniques
D026905:Amino Acid Transport Systems; D008024:Ligands; D011944:Receptors, Androgen; C475905:SLC36A1 protein, human; D027981:Symporters