A Role for Ubiquitin Binding in Bcr-Abl Transformation
Abstract
We have previously identified a docking site for ubiquitin in the amino-terminus of p210 BCR/ABL. In this proposal we have examined whether this association has implications for BCR/ABL signaling and transforming activity. Our approach was to map the binding site for ubiquitin in BCR/ABL and generate a binding mutant. The binding site is immediately adjacent to the GRB2 binding site, but the two binding activities are genetically separable. Although ubiquitin binding does not regulate BCR/ABL tyrosine kinase activity, the mutant can no longer interact with phosphorylated beta-catenin suggesting that BCR/ABL interacts with beta-catenin in a ubiquitin-dependent manner. A BCR/ABL mutant that cannot bind ubiquitin, but can still interact with Grb2, was tested for transforming activity in murine myeloid cells. The mutant can still support IL-3 independent growth in these cells indicating that some, but not all BCR/ABL activities are dependent upon this association.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jun 01, 2009
- Accession Number
- ADA510762
Entities
People
- Ian P. Whitehead
Organizations
- University of Medicine and Dentistry of New Jersey