2013年1月14日，清華大學(xué)生命科學(xué)院教授陳曄光博士應(yīng)邀訪問研究所并舉辦學(xué)術(shù)講座。講座的題目為：c-Cbl stabilizes the TGF-β type II receptor via neddylation。王曉晨博士主持講座。

Abstract:  

Transforming growth factor β (TGF-β) is a potent anti-proliferative factor in multiple types of cells.  Deregulation of TGF-β signaling is associated with development of many cancers including leukemia while the molecular mechanisms are largely unclear.  We show that c-Cbl, a known proto-oncogene encoding an ubiquitin E3 ligase, promotes TGF-β signaling by neddylating and stabilizing the type II receptor (TβRII).  Knockout of c-Cbl decreases the TβRII protein level and desensitizes hematopoietic stem/progenitor cells to TGF-β stimulation, while c-Cbl overexpression stabilizes TβRII and sensitizes leukemia cells to TGF-β.  c-Cbl conjugates NEDD8, a ubiquitin-like protein, to TβRII at Lys556 and Lys567. Neddylation of TβRII promotes its endocytosis to EEA1-positive early endosomes while prevents its endocytosis to caveolin-positive compartments, therefore inhibiting TβRII ubiquitination and degradation.  We have also identified a neddylation activity-defective c-Cbl mutation from leukemia patients, implying the link between aberrant TβRII neddylation and leukemia development.