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RSS FeedsIJMS, Vol. 20, Pages 934: Regulation of c-Raf Stability through the CTLH Complex (International Journal of Molecular Sciences)

 
 

21 february 2019 10:03:31

 
IJMS, Vol. 20, Pages 934: Regulation of c-Raf Stability through the CTLH Complex (International Journal of Molecular Sciences)
 


c-Raf is a central component of the extracellular signal-regulated kinase (ERK) pathway which is implicated in the development of many cancer types. RanBPM (Ran-Binding Protein M) was previously shown to inhibit c-Raf expression, but how this is achieved remains unclear. RanBPM is part of a recently identified E3 ubiquitin ligase complex, the CTLH (C-terminal to LisH) complex. Here, we show that the CTLH complex regulates c-Raf expression through a control of its degradation. Several domains of RanBPM were found necessary to regulate c-Raf levels, but only the C-terminal CRA (CT11-RanBPM) domain showed direct interaction with c-Raf. c-Raf ubiquitination and degradation is promoted by the CTLH complex. Furthermore, A-Raf and B-Raf protein levels are also regulated by the CTLH complex, indicating a common regulation of Raf family members. Finally, depletion of CTLH subunits RMND5A (required for meiotic nuclear division 5A) and RanBPM resulted in enhanced proliferation and loss of RanBPM promoted tumour growth in a mouse model. This study uncovers a new mode of control of c-Raf expression through regulation of its degradation by the CTLH complex. These findings also uncover a novel target of the CTLH complex, and suggest that the CTLH complex has activities that suppress cell transformation and tumour formation.


 
52 viewsCategory: Biochemistry, Biophysics, Molecular Biology
 
IJMS, Vol. 20, Pages 935: Investigating Possible Enzymatic Degradation on Polymer Shells around Inorganic Nanoparticles (International Journal of Molecular Sciences)
IJMS, Vol. 20, Pages 933: Comparative Proteomic Analysis of Wheat Carrying Pm40 Response to Blumeria graminis f. sp. tritici Using Two-Dimensional Electrophoresis (International Journal of Molecular Sciences)
 
 
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