Polypeptide that interacts with heat shock proteins

DETAILED DESCRIPTION Described herein are the isolation and characterization of a polypeptide, particularly a tetratricopeptide repeat (TPR)-containing polypeptide that is an interactive partner with heat shock proteins.
A preferred polypeptide is referred to herein as Carboxyl terminus of Hsc70-Interacting Protein or "CHIP," not only because of its ability to negatively regulate formation of heat shock protein-substrate complexes by interacting with the forward reaction cycle of heat shock proteins and other accessory chaperone cofactors, but also because the polypeptide interacts in an ATP-independent fashion with these heat shock proteins.
The nucleic acid and deduced amino acid sequences of this polypeptide in humans, mice, and Drosophila are provided.
Accordingly, the present invention provides an isolated polypeptide that negatively regulates binding of a heat shock protein to a substrate.
Preferably, the polypeptide negatively regulates the heat shock proteins Hsc70, Hsp70, and Hsp90.
The polypeptide can be a recombinant polypeptide.
The polypeptide preferably has a molecular weight of about 30 kD to about 40 kD as determined by SDS polyacrylamide gel electrophoresis.
The present invention also provides a preferred isolated polypeptide having an amino acid sequence having greater than about 40% sequence identity to that of at least one of SEQ ID NOs.
2, 7, and 8.
A particularly preferred polypeptide contains at least amino acids 1 197 from any of the polypeptides of SEQ ID NOs.
2, 7, and 8 is capable of negatively regulating the binding of a heat shock protein to a substrate.
The polypeptide can be recombinant.
In another preferred embodiment, the present invention further provides an isolated polypeptide having an amino acid sequence represented by at least one of SEQ ID NOs.
2, 7, and 8.
Preferably, the polypeptide is capable of negatively regulating the binding of a heat shock protein to a substrate.
The polypeptide can be recombinant.
In another preferred embodiment, the present invention also provides a polypeptide containing an amino acid sequence represented by at least one of SEQ ID NOs