title: Mutant Cbl proteins as oncogenic drivers in myeloproliferative disorders.
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.
authors.affiliation: Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, NE, USA. mnaramura@unmc.edu
authors.forename: Mayumi
authors.initials: M
authors.lastname: Naramura
authors.forename: Scott
authors.initials: S
authors.lastname: Nadeau
authors.forename: Bhopal
authors.initials: B
authors.lastname: Mohapatra
authors.forename: Gulzar
authors.initials: G
authors.lastname: Ahmad
authors.forename: Chandrani
authors.initials: C
authors.lastname: Mukhopadhyay
authors.forename: Martin
authors.initials: M
authors.lastname: Sattler
authors.forename: Srikumar M
authors.initials: SM
authors.lastname: Raja
authors.forename: Amarnath
authors.initials: A
authors.lastname: Natarajan
authors.forename: Vimla
authors.initials: V
authors.lastname: Band
authors.forename: Hamid
authors.initials: H
authors.lastname: Band
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002471:Cell Transformation, Neoplastic / Q000235:genetics* / Q000378:metabolism; D005786:Gene Expression Regulation; D019337:Hematologic Neoplasms / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008969:Molecular Sequence Data; D009196:Myeloproliferative Disorders / Q000235:genetics* / Q000378:metabolism; D050721:Proto-Oncogene Proteins c-cbl / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction; D054875:Ubiquitination
chemical_list: D050721:Proto-Oncogene Proteins c-cbl