DIMERIZATION OF MAMMALIAN PROGESTERONE RECEPTORS OCCURS IN THE ABSENCE OF DNA AND IS RELATED TO THE RELEASE OF THE 90-KDA HEAT-SHOCK PROTEIN
DIMERIZATION OF MAMMALIAN PROGESTERONE RECEPTORS OCCURS IN THE ABSENCE OF DNA AND IS RELATED TO THE RELEASE OF THE 90-KDA HEAT-SHOCK PROTEIN
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DOI：
10.1073/pnas.88.1.72
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发表时间：
1991-01-01
影响因子：
11.1
通讯作者：
EDWARDS, DP
中科院分区：
文献类型：
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作者：
DEMARZO, AM;BECK, CA;EDWARDS, DP
在这项研究中，我们证明了哺乳动物孕激素受体(PR)的二聚化是在没有DNA的情况下发生的。用抗全长B型孕激素受体(PR-B)的单抗对T-47D人乳腺癌细胞提取液进行了特异性免疫共分离试验。这导致大量截短型-A受体(PR-A)的共分离，表明溶液中存在稳定的PR-A-PR-B二聚体。不同受体形式在溶液中齐聚的能力与不同受体形式在溶液中齐聚的能力以及它们与特定DNA序列的结合能力之间存在正相关。在没有DNA的情况下形成稳定的PR-A-PR-B寡聚体的能力也被发现与从未激活的PR复合体释放90-kDa热休克蛋白(HSP90)有关。这些结果支持这一假说，即在没有DNA的情况下二聚化是控制受体DNA结合功能的重要机制，HSP90的释放可能是调节二聚化的关键步骤。这提示HSP90可能通过阻断受体二聚化而间接抑制DNA结合活性。
In this study we have demonstrated that dimerization of mammalian progesterone receptors (PR) occurs in the absence of DNA. A specific immune coisolation assay was performed on extracts of T-47D human breast cancer cells with a monoclonal antibody specific for the full-length B form of progesterone receptor (PR-B). This resulted in coisolation of significant amounts of truncated form-A receptors (PR-A), indicating the presence of stable PR-A-PR-B dimers in solution. A positive correlation was observed between the ability of different receptor forms to oligomerize in solution and their ability of different receptor forms to oligomerize in solution and their ability to bind to specific DNA sequences. The ability to form stable PR-A-PR-B oligomers in the absence of DNA was also found to correlate with release of 90-kDa heat shock protein (hsp90) from the unactivated PR complex. These results support the hypothesis that dimerization in the absence of DNA is an important mechanism controlling receptor DNA-binding function and that hsp90 release may be a key step regulating dimerization. This suggests that hsp90 may function to repress DNA-binding activity indirectly by blocking receptor dimerization.