A Role for Ubiquitin Binding in Bcr-Abl Transformation
Annual rept. 1 Jun 2007-31 May 2008
UNIVERSITY OF MEDICINE AND DENTISTRY OF NEW JERSEY NEWARK
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We have previously identified a docking site for ubiquitin in the amino-terminus of p210 BCRABL. Since ubiquitin binding has been implicated in both the intra- and inter-molecular regulation of many signaling molecules this association may have important clinical consequences for chronic myelogenous leukemia. During Year 1 of this study, we have precisely mapped the binding site for ubiquitin and generated a p210 BCRABL mutant that is completely impaired in binding in mammalian cells. Loss of ubiquitin binding does not destabilize p210 BCRABL thus allowing us to directly evaluate the mutant in assays for leukemogenic activity. This mutant will provide us with a unique opportunity to directly assess the importance of the ubiquitin-p210 BCRABL interaction in CML. These studies will be performed in Year 2 of this study.
- Medicine and Medical Research