Insecticide Exposure in Parkinsonism
Abstract
The EGFR receptor tyrosine kinase is dysfunctional in a wide range of solid human tumors including prostate carcinomas. The EGFR gene product is a transmembrane glycoprotein belonging to the epidermal growth factor receptor family and its cytoplasmic domain is responsible for sending the mitogenic signals into cells. We discovered that this domain of EGFR interacts with Tidl protein, a human counterparts of Drosophila tumor suppressor Tid56. Tid56 null mutation causes lethal tumorigenesis during larvae stage. Tidl is also known as a cochaperone of the heat shock protein 70 (Hsp70) and binds to Hsp70 through its conserved DnaJ-domain. We found that Increased expression of Tidl in human carcinoma attenuate's the EGFR-dependent oncogenic ERK1/2 and BMKl signaling pathways. Importantly, the functional DnaJ-domain of Tidl is required for consequent suppression of oncogenic signaling of carcinoma cells resulting from increased Tidl expression. Together, these results suggest that Tidl deterring controlled proliferation of carcinoma cells through reducing the downregulating the cancerous signaling from EGFR. Moreover, the cochaperonic and regulatory function of Tidl on Hsp70 most likely play an essential role of this anti- proliferation function of Tidl in carcinoma cells.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jan 01, 2004
- Accession Number
- ADA423195
Entities
People
- Bradley G. Klein
- Jeffery R Bloomquist