The invention relates to assays for screening for chemicals which affect
the binding between proteins comprising an SH3 binding motif (such as
Proline-rich Nuclear Receptor Co-regulatory protein (PNRC)) and nuclear
receptor proteins. Compounds which affect the binding of PNRC to nuclear
receptors can affect the expression of genes whose expression is under
the control of nuclear receptors to which PNRC binds. PNRC interacts with
the orphan receptors SF1 and ERR.alpha.1 in a ligand-independent manner
and interacts with the ligand-binding domains of nuclear receptors such
as ER, AR, PR, TR, BAR, and RXR in a ligand-dependent manner. A 23-amino
acid region in the carboxy-terminal proline-rich region which contains an
SH3-binding motif is sufficient for the interaction with nuclear
receptors.