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Submitted on May 2, 2002
Accepted on October 22, 2002
1 Department s of Cellular & Structural Biologyand Molecular Medicine, The University of Texas Health, Science Center at San Antonio, 15355 Lambda Drive, San Antonio, TX 78245-3207, and South Texas Veterans Health Care System, 7400 Merton Minter Boulevard, San Antonio, TX 78229
* To whom correspondence should be addressed. E-mail: roy{at}uthscsa.edu.
The dynamic interaction between the androgen receptor (AR) and steroid receptor coactivator-1 (SRC-1) was explored in living cells expressing chimeric forms of the receptor and the coactivator containing two spectral variants of jellyfish fluorescent protein. Laser scanning confocal imaging of transfected cells expressing fluorescently labeled SRC-1 revealed that in an unsynchronized cell population, the coactivator is distributed in 
40% cells as nuclear bodies of 0.2 to 1.0 µm in diameter. Immunostaining of cyan fluorescent protein labeled SRC-1 (CFP-SRC1) expressing cells with antibody to PML protein showed significant overlap of the CFP fluorescence with the antibody stain. Cotransfection of cells with a plasmid expressing the cyan fluorescent protein (CFP) conjugate of Sp100 (another marker protein for the PML nuclear body) also showed colocalization of the YFP-SRC1 containing nuclear foci with the PML bodies in living cells. Analysis of the three dimensional structure revealed that the PML bodies are round to elliptical in shape with multiple satellite bodies on their surface. Some of these satellite bodies contain the SRC-1. Activation and nuclear import of CFP-AR by the agonistic ligand 5
-dihydrotestosterone (DHT), but not by the antagonist casodex, transferred YFP-SRC1 from the PML bodies to an interlacing filamentous structure. In a single living cell, agonist activated AR caused a time-dependent movement of YFP-SRC1 from the PML bodies to this filamentous structure. Additionally, coexpression of a constitutively active mutant of AR (AR-
LBD) also displaced YFP-SRC1 from the PML bodies to this intranuclear filamentous structure. The fluorescence recovery after photobleaching (FRAP) approach was used to examine changes in the kinetics of movement of YFP-SRC1 during its mobilization from the PML bodies to the intranuclear filamentous structure by the agonist activated AR. Results of the relative half-times (t
) of replacement of YFP-SRC1 within the photobleached region of a single PML body from its surrounding nuclear space supported the conclusion that SRC-1 is actively transported from the PML bodies to the intranuclear filamentous structure by the ligand activated AR. This observation also suggests an interaction between AR and SRC-1 before its binding to the target gene. The PML bodies have been implicated as a crossroad for multiple regulatory pathways that control cell proliferation, cellular senescence and apoptosis. Our present results along with other recent reports expand the role of this subnuclear structure to include the regulation of steroid hormone action.
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