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

Zonghan Dai, Robert C. Quackenbush, Kevin D. Courtney, Matthew Grove, David Cortez, Gary W. Reuther, Ann Marie Pendergast

Research output: Contribution to journalArticle

98 Scopus citations

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 languageEnglish (US)
Pages (from-to)1415-1424
Number of pages10
JournalGenes and Development
Volume12
Issue number10
DOIs
StatePublished - May 15 1998

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Keywords

  • Abi
  • Bcr-Abl
  • Ph-positive leukemia
  • Ubiquitin-dependent proteolysis
  • V-Src

ASJC Scopus subject areas

  • Genetics
  • Developmental Biology

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