Oncogenic Abl and Src tyrosine kinases elicit the ubiquitin-dependent degradation of target proteins through a Ras-independent pathway.

Dai Z, Quackenbush RC, Courtney KD, Grove M, Cortez D, Reuther GW, Pendergast AM
Genes Dev. 1998 12 (10): 1415-24

PMID: 9585502 · PMCID: PMC316832 · DOI:10.1101/gad.12.10.1415

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 ubiquitin-proteasome pathway.

MeSH Terms (22)

Adaptor Proteins, Signal Transducing Animals Bone Marrow Cysteine Endopeptidases Cytoskeletal Proteins Fusion Proteins, bcr-abl Gene Expression Regulation, Leukemic Homeodomain Proteins Humans Leukemia Leukemia, Myelogenous, Chronic, BCR-ABL Positive Mice Multienzyme Complexes Neoplasm Proteins Precursor B-Cell Lymphoblastic Leukemia-Lymphoma Proteasome Endopeptidase Complex Protein Processing, Post-Translational Proto-Oncogene Proteins c-abl Proto-Oncogene Proteins pp60(c-src) ras Proteins Tumor Cells, Cultured Ubiquitins

Connections (1)

This publication is referenced by other Labnodes entities:

Links