Simian virus 40 small t antigen mediates conformation-dependent transfer of protein phosphatase 2A onto the androgen receptor.
The tumor antigens simian virus 40 small t antigen (ST) and polyomavirus small and medium T antigens mediate cell transformation in part by binding to the structural A subunit of protein phosphatase 2A (PP2A). The replacement of B subunits by tumor antigens inhibits PP2A activity and prolongs phosphorylation-dependent signaling. Here we show that ST mediates PP2A A/C heterodimer transfer onto the ligand-activated androgen receptor (AR). Transfer by ST is strictly dependent on the agonist-activated conformation of AR, occurs within minutes of the addition of androgen to cells, and can occur in either the cytoplasm or the nucleus. The binding of ST changes the conformation of the A subunit, and ST rapidly dissociates from the complex upon PP2A A/C heterodimer binding to AR. PP2A is transferred onto the carboxyl-terminal half of AR, and the phosphatase activity is directed to five phosphoserines in the amino-terminal activation function region 1, with a corresponding reduction in transactivation. Thus, ST functions as a transfer factor to specify PP2A targeting in the cell and modulates the transcriptional activity of AR.
Yang
Chun-Song
CS
Center for Cell Signaling, University of Virginia, Box 800577 Health Systems, Charlottesville, VA 22908, USA.
Vitto
Michael J
MJ
Busby
Scott A
SA
Garcia
Benjamin A
BA
Kesler
Cristina T
CT
Gioeli
Daniel
D
Shabanowitz
Jeffrey
J
Hunt
Donald F
DF
Rundell
Kathleen
K
Brautigan
David L
DL
Paschal
Bryce M
BM
D000728:Androgens / Q000378:metabolism; D000818:Animals; D000957:Antigens, Viral, Tumor / Q000378:metabolism*; D019556:COS Cells; D002467:Cell Nucleus; D002522:Chlorocebus aethiops; D003593:Cytoplasm; D006801:Humans; D008297:Male; D010749:Phosphoprotein Phosphatases / Q000378:metabolism*; D010766:Phosphorylation; D011471:Prostatic Neoplasms; D011487:Protein Conformation; D054648:Protein Phosphatase 2; D021122:Protein Subunits / Q000378:metabolism*; D011944:Receptors, Androgen / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D013539:Simian virus 40 / Q000378:metabolism*; D015533:Transcriptional Activation / Q000502:physiology; D014407:Tumor Cells, Cultured
D000728:Androgens; D000957:Antigens, Viral, Tumor; D021122:Protein Subunits; D011944:Receptors, Androgen; D010749:Phosphoprotein Phosphatases; D054648:Protein Phosphatase 2