| Molecular chaperones are ubiquitous and abundant proteins that regulate many biological processes. They help proteins to fold correctly by binding to the exposed hydrophobic residues of polypeptides and shifting the equilibrium away from aggregation. Molecular chaperones are also involved in processes such as translocation of proteins into organelles, degradation, and signal transduction.; Studies demonstrate that chaperones play critical roles in the maintenance of nuclear receptors and the activation of protein kinases. Two members of the heat shock protein family, Hsp70 and Hsp90, interact with their co-chaperones to mediate efficient protein folding. The relationship between these co-chaperones is complicated and they exist in discrete complexes.; In this thesis, I will characterize the roles of different Hsp90 co-chaperones in the activation of protein kinases, v-Src and Ste11 and a nuclear receptor, the androgen receptor. One of the main focus of my thesis involves a protein called Cdc37. Although its importance as a chaperone has been established, it was still unclear how it was recruited into the folding pathway of a protein. By using both yeast genetics and biochemistry, I hypothesize that an Hsp70 and Hsp co-chaperone known as Sti1 recruits Cdc37 to protein kinases.; Androgen receptor possesses unique properties that make it an exception in its steroid hormone receptor superfamily regarding Cdc37's involvement. The functional roles played by Cdc37 and Ydj1's domains in androgen receptor activation are the focus of my last study. |
