Cbl and Human Myeloid Neoplasms: The Cbl Oncogene Comes of Age
Open Access
- 14 June 2010
- journal article
- review article
- Published by American Association for Cancer Research (AACR) in Cancer Research
- Vol. 70 (12), 4789-4794
- https://doi.org/10.1158/0008-5472.can-10-0610
Abstract
Cbl was originally discovered in 1989 as the cellular homolog of the v-Cbl oncogene, the transforming gene of the Cas NS-1 murine retrovirus that causes myeloid leukemia and lymphomas in mice. Cbl is a member of a family of RING finger ubiquitin ligases that negatively regulate signaling by tyrosine kinases and that function as adaptor proteins to regulate signaling positively. Until the past 2 years, there was little evidence that Cbl proteins were involved in human malignancies. Recent publications have shown homozygous mutations in Cbl in human myeloid neoplasms. Although in vitro and animal transformation models suggested that mutant forms of Cbl acted as an oncogene, the cellular role suggested that the protein could serve as a tumor suppressor gene. The recent data begin to reconcile this paradox as the loss of ubiquitin ligase function (the tumor suppressor function) is coupled to the maintenance of the positive signaling function (the oncogene function). These data also provide insight into potential therapeutic approaches to myeloid disorders harboring Cbl mutations. Cancer Res; 70(12); 4789–94. ©2010 AACR.This publication has 32 references indexed in Scilit:
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