Turkish Neurosurgery 2010-07-01

PKC alpha phosphorylates cytosolic NF-kappaB/p65 and PKC delta delays nuclear translocation of NF-kappaB/p65 in U1242 glioblastoma cells.

Melike Mut, Samson Amos, Isa M Hussaini

文献索引：Turk. Neurosurg. 20(3) , 277-85, (2010)

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摘要

Protein kinase-C (PKC) and NF-kappaB are involved in cell survival, proliferation, migration and radioresistance in glioblastoma multiforme (GBM). We sought to determine the interaction between PKC and NF-kappaB pathways.The activation of NF-kappaB by PKC alpha and PKC delta was assessed by Western blotting after the stimulation with Phorbol 12- Myristate 13-Acetate (PMA). Gene silencing of PKC alpha , PKC delta and NFkappaB/ p65 with siRNA interference was utilized to evaluate their roles in NFkB activation and cell proliferation.PMA induced the phosphorylation of NF-kappaB/p65 by PKC alpha. Gene silencing with siRNA against NF-kappaB/p65 inhibited [3H]-thymidine incorporation in U1242 GBM cells. PKC delta decelerated the nuclear translocation of activated NF-kappaB/p65 up to 4 hours after the stimulation. PMA induced death was not observed in PKC delta silenced cells where activated NF-kappaB/p65 was located immediately in the nucleus.NF-kappaB/p65 is pro-survival and proliferative factor in U1242 GBM cells. PKC alpha is needed to phosphorylate NF-kappaB/p65. PKC delta delays the translocation of active NF-kappaB/p65 into the nucleus. PMA-induced cell death occurred if the phospho-NF-kappaB/p65 was prohibited from entering the nucleus in PKC delta positive cells. Translocation of phosphorylated form of NF-kappaB into the nucleus is critical in GBM cell proliferation.