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Editorial
. 2015 Oct;17(10):1305-6.
doi: 10.1093/neuonc/nov165.

Neddylation in glioblastomas

Sheila Mansouri  1 , Gelareh Zadeh  1
Affiliations
Editorial

Neddylation in glioblastomas

Sheila Mansouri et al. Neuro Oncol. 2015 Oct.
No abstract available

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Figures

Fig. 1.
Fig. 1.
An overview of posttranslational NEDDylation of cullin (CUL) and its disruption by MLN4924. NEDDylation of CUL involves the transfer of the ubiquitin-like molecule NEDD8 (neural precursor cell expressed, developmentally downregulated 8) to CUL by NEDD8-activating enzyme E1 (NAE), NEDD8 conjugating enzyme E2 (UBE2M/Ubc12, UBE2F), and the NEDD8-E3 ligase cascade. MLN4924 is a highly potent and selective first-in-class inhibitor of NAE activity that covalently binds to the active site of the NAE and leads to inactivation of CRL and accumulation of its substrates, including tumor suppressor proteins p21 and p27 (A). Treatment of glioma cell lines with MLN4924 results in inhibition of cell cycle progression at the G2 phase and induction of apoptosis or senescence in a cell line-dependent manner. Administration of MLN4924 to an orthotopic xenograft model of glioblastoma (GBM) causes formation of smaller tumors expressing lower levels of proliferation marker Ki67 and increased amounts of the cell cycle regulator protein p21. This study identifies a potential new drug for targeting GBMs through specific inhibition of NAE.
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Comment on

References

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