Oncoprotein p28 GANK binds to RelA and retains NF-kappaB in the cytoplasm through nuclear export.
p28(GANK) (also known as PSMD10, p28 and gankyrin) is an ankyrin repeat anti-apoptotic oncoprotein that is commonly overexpressed in hepatocellular carcinomas and increases the degradation of p53 and Rb. NF-kappaB (nuclear factor-kappaB) is known to be sequestered in the cytoplasm by I kappaB (inhibitor of NF-kappaB) proteins, but much less ... is known about the cytoplasmic retention of NF-kappaB by other cellular proteins. Here we show that p28(GANK) inhibits NF-kappaB activity. As a nuclear-cytoplasmic shuttling protein, p28(GANK) directly binds to NF-kappaB/RelA and exports RelA from nucleus through a chromosomal region maintenance-1 (CRM-1) dependent pathway, which results in the cytoplasmic retention of NF-kappaB/RelA. We demonstrate that all the ankyrin repeats of p28(GANK) are required for the interaction with RelA and that the N terminus of p28(GANK), which contains the nuclear export sequence (NES), is responsible for suppressing NF-kappaB/RelA nuclear translocation. These results suggest that overexpression of p28(GANK) prevents the nuclear localization and inhibits the activity of NF-kappaB/RelA.
Mesh Terms:
Active Transport, Cell Nucleus, Ankyrin Repeat, Cell Nucleus, Cytoplasm, Enzyme Activation, Humans, NF-kappa B, Nuclear Export Signals, Proteasome Endopeptidase Complex, Protein Binding, Proto-Oncogene Proteins, RNA, Small Interfering, Transcription Factor RelA
Active Transport, Cell Nucleus, Ankyrin Repeat, Cell Nucleus, Cytoplasm, Enzyme Activation, Humans, NF-kappa B, Nuclear Export Signals, Proteasome Endopeptidase Complex, Protein Binding, Proto-Oncogene Proteins, RNA, Small Interfering, Transcription Factor RelA
Cell Res.
Date: Dec. 01, 2007
PubMed ID: 18040287
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