2013年1月14日，清华大学生命科学院教授陈晔光博士应邀访问研究所并举办学术讲座。

2013年1月14日，清华大学生命科学院教授陈晔光博士应邀访问研究所并举办学术讲座。讲座的题目为：c-Cbl stabilizes the TGF-β type II receptor via neddylation。王晓晨博士主持讲座。

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.