期刊
MOLECULAR BIOLOGY OF THE CELL
卷 23, 期 14, 页码 2635-2644出版社
AMER SOC CELL BIOLOGY
DOI: 10.1091/mbc.E11-09-0805
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资金
- National Basic Research Program of China (973 program) [2011CB910604, 2012CB822104]
- National Natural Science Foundation of China [31070723, 81172879]
- Key Project Natural Science Foundation of Jiangsu province [11KJA310002]
- Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD)
The Notch signaling regulator Numblike (Numbl) is expressed in the brain, but little is known regarding its role in the pathophysiology of glial cells. In this paper, we report that Numbl expression was down-regulated in high-grade human glioma tissue samples and glioblastoma cell lines. To investigate the role of Numbl in glioma migration and invasion, we generated human glioma cell lines in which Numbl was either overexpressed or depleted. Overexpression of Numbl suppressed, while elimination of Numbl promoted, the migration and invasion of glioma cells. Numbl inhibited glioma migration and invasion by dampening NF-kappa B activity. Furthermore, Numbl interacted directly with tumor necrosis factor receptor-associated factor 5 (TRAF5), which signals upstream and is required for the activation of NF-kappa B, and committed it to proteasomal degradation by promoting K48-linked polyubiquitination of TRAF5. In conclusion, our data suggest that Numbl negative regulates glioma cell migration and invasion by abrogating TRAF5-induced activation of NF-kappa B.
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