Mutant Cbl proteins as oncogenic drivers in myeloproliferative disorders

Oncotarget. 2011 Mar;2(3):245-50. doi: 10.18632/oncotarget.233.

Abstract

Casitas B-lineage lymphoma (Cbl) family proteins are evolutionarily-conserved attenuators of protein tyrosine kinase (PTK) signaling. Biochemical analyses over the past two decades have firmly established that the negative regulatory functions of Cbl proteins are mediated through their ability to facilitate ubiquitination and thus promote degradation of PTKs. As aberrant activation of PTKs is frequently associated with oncogenesis, it has long been postulated that loss of normal Cbl functions may lead to unregulated activation of PTKs and cellular transformation. In the last few years, mutations in the CBL gene have been identified in a subset of human patients with myeloid malignancies. Here we discuss insights gained from the analyses of Cbl mutants both in human patients and in animal models and propose potential mechanisms of oncogenesis through this pathway.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Cell Transformation, Neoplastic / genetics*
  • Cell Transformation, Neoplastic / metabolism
  • Gene Expression Regulation
  • Hematologic Neoplasms / genetics*
  • Hematologic Neoplasms / metabolism
  • Humans
  • Molecular Sequence Data
  • Myeloproliferative Disorders / genetics*
  • Myeloproliferative Disorders / metabolism
  • Proto-Oncogene Proteins c-cbl / genetics*
  • Proto-Oncogene Proteins c-cbl / metabolism
  • Signal Transduction
  • Ubiquitination

Substances

  • Proto-Oncogene Proteins c-cbl