Cytoplasmic retention, DNA binding and processing of the NF-kappa B p50 precursor are controlled by a small region in its C-terminus.
The transcription factor NF-kappa B binds to DNA as a heterodimer composed of two subunits of 50 kDa (p50) and 65 kDa (p65). p50 contains a DNA binding and dimerization domain and represents a truncated form of a 105 kDa (p105) precursor molecule. We show here that in different cell types the p105 precursor as well as the processed p50 coexist in the cytoplasm, but that only the latter enters the nucleus. The cytoplasmic retention of the precursor molecule is controlled by a small region in its C-terminal part. We show that this region is responsible for the observed lack of DNA binding of the p50 precursor and controls the extent of processing of the precursor to the mature form. We also present evidence that a stretch of four basic amino acids, similar to a sequence found in the other proteins belonging to the rel/NF-kappa B family, is required for translocation of the processed p50 protein into the nucleus and thus could be the target for the retention mechanism.
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Unité de Biologie Moléculaire du Géne, U 277 INSERM, UA 535 CRNS, Institut Pasteur, Paris, France.
Kourilsky
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Israël
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D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism*; D004247:DNA / Q000378:metabolism*; D005455:Fluorescent Antibody Technique; D000882:Haplorhini; D006367:HeLa Cells; D006801:Humans; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D052002:NF-kappa B p50 Subunit; D011233:Precipitin Tests; D011498:Protein Precursors / Q000235:genetics / Q000378:metabolism*; D011499:Protein Processing, Post-Translational; D014162:Transfection
D016328:NF-kappa B; D052002:NF-kappa B p50 Subunit; D011498:Protein Precursors; D004247:DNA