Accumulation of the GSK3 target protein β-catenin is lethal for B cell precursors and malignant B cells
Jumaa, H.; Kistner, K. M.; Setz, C.; Taketo, M. M.; Jumaa, H.; Jellusova, J.
Show abstract
Glycogen synthase kinase 3 (GSK3) is a ubiquitously expressed kinase involved in a myriad of biological processes. Although GSK3 mediated phosphorylation has been shown to induce the degradation of many pro-survival and pro-proliferation factors, cancer cells of different origin show reduced proliferation or survival after GSK3 inhibition. Our current understanding of the role GSK3 plays in normal mature B cells, B cell precursors and transformed B cells is incomplete and does not allow to assess whether GSK3 inhibitors can be used to treat B cell derived malignancies. Here we identify {beta}-catenin as the major factor driving GSK3-inhibition induced changes in B cells. We show that {beta}-catenin accumulation has opposing effects on cell metabolism and survival in mature B cells and B cell precursors. Moreover, we demonstrate that {beta}-catenin destabilizes the commitment to the B cell lineage. In summary, our study identifies {beta}-catenin induced signaling as a factor that can be exploited to limit the survival of malignant B cells.
Matching journals
The top 6 journals account for 50% of the predicted probability mass.