Role of Cdc37 in Breast Cancer
Abstract
P50CdC37 functions in the establishment of protein kinase signaling pathways by functioning in complex with molecular chaperone Hsp90. Biochemical and genetic data indicate that Cdc37/Hsp90 complex plays a central role in the establishment of pathways that are directly implicated in cell cycle promotion and transformation. The proposed mode of function of Cdc37/Hsp90 complex is that Cdc37 targets intrinsically unstable kinases to the complex with Hsp90, and this transient interaction of newly synthesized kinases with the complex is necessary for their stabilization and/or folding and further activation. Multiple oncoproteins have been shown to require Hsp90/Cdc37 function for their stability. To test the hypothesis predicting that Cdc37 expression would be required for proliferative aspects of development and for cell proliferation induced by oncogenes, we created and analyzed a transgenic mouse model where Cdc37 expression is driven by MMTV promoter, directing the expression into breast epithelial cells, salivary and lacrimal gland, as well in some other organs. Our study show that Cdc37 is a first identified chaperone functioning as an oncogene, and is capable of cooperating with other oncogenes such as c-myc and neu for transformation.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 1999
- Accession Number
- ADA375119
Entities
People
- Lilia J. Stepanova
Organizations
- Baylor College of Medicine