Abstract
Oncogenic forms of the Abl and Src tyrosine kinases trigger the destruction of the Abi proteins, a family of Abl-interacting proteins that antagonize the oncogenic potential of Abl after overexpression in fibroblasts. The destruction of the Abi proteins requires tyrosine kinase activity and is dependent on the ubiquitin-proteasome pathway. We show that degradation of the Abi proteins occurs through a Ras-independent pathway. Significantly, expression of the Abi proteins is lost in cell lines and bone marrow cells isolated from patients with aggressive Bcr-Abl-positive leukemias. These findings suggest that loss of Abi proteins may be a component in the progression of Bcr-Abl-positive leukemias and identify a novel pathway linking activated nonreceptor protein tyrosine kinases to the destruction of specific target proteins through the ubiquitinproteasome pathway.
Original language | English (US) |
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Pages (from-to) | 1415-1424 |
Number of pages | 10 |
Journal | Genes and Development |
Volume | 12 |
Issue number | 10 |
DOIs | |
State | Published - May 15 1998 |
Keywords
- Abi
- Bcr-Abl
- Ph-positive leukemia
- Ubiquitin-dependent proteolysis
- V-Src
ASJC Scopus subject areas
- Genetics
- Developmental Biology