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

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Dai, Z; Quackenbush, RC; Courtney, KD; Grove, M; Cortez, D; Reuther, GW; Pendergast, AM

Published Date

  • May 15, 1998

Published In

Volume / Issue

  • 12 / 10

Start / End Page

  • 1415 - 1424

PubMed ID

  • 9585502

International Standard Serial Number (ISSN)

  • 0890-9369

Language

  • eng

Conference Location

  • United States