TI  - Interactions of   <prot>p60</prot>  , a mediator of <prot>progesterone receptor</prot> assembly, with
      heat shock proteins  <prot>hsp90</prot>  and  <prot>hsp70</prot> .
PG  - 682-93
AB  - Previous studies on the assembly of <prot>progesterone receptor</prot> (<prot>PR</prot>) complexes
      in vitro have suggested that <prot>PR</prot> assembly is a dynamic, ordered process
      involving at least eight nonreceptor proteins. One of these proteins, <prot>p60</prot>,
      appears transiently during assembly and is not a component of functionally
      mature <prot>PR</prot> complexes. In the present study we observe that a monoclonal
      antibody specific for <prot>p60</prot> can, on the one hand, inhibit formation of
      mature <prot>PR</prot> complexes containing <prot>heat shock protein 90</prot> (<prot>hsp90</prot>), <prot>p23</prot>, and
      immunophilins and, on the other, enhance recovery of early <prot>PR</prot> complexes
      containing <prot>hsp70</prot> and <prot>Hip</prot> (<prot>p48</prot>). This observation supports a model in which
      <prot>p60</prot> functions at an intermediate stage of <prot>PR</prot> assembly to facilitate
      formation of subsequent <prot>PR</prot> complexes lacking <prot>p60</prot>. Since  <prot>p60</prot>  is typically
      found in a complex with  <prot>hsp90</prot>  and  <prot>hsp70</prot> , we have further characterized its
      interactions with these proteins.   <prot>P60</prot>   can bind either  <prot>hsp70</prot>  or  <prot>hsp90</prot> 
      independently and in an ATP-independent manner. Since <prot>hsp90</prot> and <prot>hsp70</prot> do
      not readily associate on their own, it appears that <prot>p60</prot> is the central
      organizing component of an  <prot>hsp90</prot> - <prot>p60</prot> - <prot>hsp70</prot>  complex. Mutational analysis of
         <prot>p60</prot>    indicates that the N terminus is required for  <prot>hsp70</prot>  binding, and a
      central region containing tetratricopeptide repeat motifs is necessary for
      binding  <prot>hsp90</prot>  and  <prot>hsp70</prot> . The  <prot>hsp90</prot> - <prot>p60</prot> - <prot>hsp70</prot>  multichaperone complex is
      highly dynamic and does not appear to be affected by the <prot>hsp90</prot>-binding
      drug geldanamycin. The interactions of  <prot>hsp70</prot>  and  <prot>hsp90</prot>  in intermediate <prot>PR</prot>
      complexes are shown to be distinct from their separate interactions in
      early <prot>PR</prot> complexes (<prot>hsp70</prot>) or in mature <prot>PR</prot> complexes (hsp90). From these
      results, it appears that <prot>p60</prot> is a key mediator in the chaperoned assembly
      and functional maturation of <prot>PR</prot> complexes.
AD  - Department of Pharmacology, University of Nebraska Medical Center, Omaha
