Endoproteolytic processing of C-terminally truncated NF-kappaB2 precursors at kappaB-containing promoters.
The C-terminal, partially truncated forms of the NF-kappaB2/p52 precursor p100, p100DeltaCs, manifest constitutive processing and oncogenic ability, although the responsible mechanisms remain unknown. Here, we report that p100DeltaCs are specifically processed in association with binding to promoter DNA-containing kappaB sites. In the nucleus, p100DeltaCs bind to the kappaB promoter DNA and subsequently recruit the proteasome to form a stable proteasome/p100DeltaC/DNA complex, which mediates the processing of p100DeltaCs. Notably, the processing at the kappaB promoter is initiated by a proteasome-mediated endoproteolytic cleavage at amino acid D(415) of p100DeltaCs, and the processed p52, but not the precursors themselves, is oncogenic by up-regulating a subset of target genes. Our studies demonstrate a different mechanism of p100 processing and also present evidence showing that the proteasome modulates the action of transcription factors at promoter regions through endoproteolysis.
Qing
Guoliang
G
Department of Cell Biology and Neuroscience, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USA.
Qu
Zhaoxia
Z
Xiao
Gutian
G
D002467:Cell Nucleus / Q000378:metabolism; D004247:DNA / Q000737:chemistry; D003720:Densitometry; D006367:HeLa Cells; D006801:Humans; D008957:Models, Genetic; D009154:Mutation; D052003:NF-kappa B p52 Subunit / Q000235:genetics* / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D011401:Promoter Regions, Genetic; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D014158:Transcription, Genetic; D014162:Transfection
D052003:NF-kappa B p52 Subunit; C498206:NFKB2 protein, human; D004247:DNA; D046988:Proteasome Endopeptidase Complex