Regulation of EGF Receptor Signaling by Histone Deacetylase 6 (HDAC6)-Mediated Reversible Acetylation
Abstract
One of the hallmarks of cancer is uncontrolled cell growth and proliferation. In cells, a group of proteins called growth factor receptors are responsible for responding to the signals that trigger proliferation. When these receptors function abnormally due to genetic mutation, these can undergo uncontrolled proliferation and become cancerous. In the case of breast cancer, a specific group of growth factor receptors, the ErbB family, have been implicated in the formation of tumors. In order to prevent uncontrolled growth, normal cells tightly regulate the activity of the EGF receptors. Upon their activation, which initiates the signaling that triggers cell proliferation, the receptor is also programmed to be destroyed in order to stop growth factor-induced signaling. A defect in this destructive mechanism can result in abnormally active EGFR, which can lead to uncontrolled signaling, and thus tumor formation. Recently, it has been shown that Hsp90 (heat shock protein 90) is able to bind EGFR, and prevent its destruction. Tile ability of Hsp90 to bind substrate proteins appears to be regulated by a small chemical modification termed reversible acetylation. Hsp9O appears to require deacetylation in order to properly interact with its substrates. This would suggest that the modulation of Hsp9O acetylation status will be important for EGFR-mediated cell proliferation. Our lab has found that Hsp90 interacts with HDAC6 (histone deacetylase 6), which is a protein that acts to remove acetyl groups from proteins (deacetylation), and we hypothesize that this interaction plays a regulatory role in EGFR functioning. We aim to characterize the interaction between these proteins, and determine how this interaction effects EGFR signaling. In addition, we will examine the role of HDAC6 in EGFR-mediated breast cancer formation in a tissue culture model.
Document Details
- Document Type
- Technical Report
- Publication Date
- Apr 01, 2005
- Accession Number
- ADA435267
Entities
People
- Jeffrey J. Kovacs
Organizations
- Duke University