title: Intramolecular masking of the nuclear location signal and dimerization domain in the precursor for the p50 NF-kappa B subunit.
abstract: We show that the non-DNA-binding precursor for the p50 subunit (p110), like NF-kappa B, is subject to control of nuclear uptake. In contrast to p50, p110 was excluded from nuclei and unable to associate detectably with p50 or p65 NF-kappa B subunits. The nuclear location signal in the N-terminal half of p110 was not accessible for monospecific antibodies. Removal of only 191 amino acids from the C-terminus of p110 restored antibody accessibility as well as nuclear uptake. The C-terminal half of p110, which is linked to the p50 portion via a glycine-rich hinge, could also noncovalently bind to p50. This helps to explain why p50, after cleavage of the precursor in intact cells, was still retained in an inactive form in the cytoplasm. Our study describes a novel mechanism of nuclear uptake control by masking of a nuclear location signal through a remote domain within a precursor molecule.
authors.affiliation: Laboratorium für Molekulare Biologie, Ludwig-Maximilians-Universität München, Martinsried, Federal Republic of Germany.
authors.forename: T
authors.initials: T
authors.lastname: Henkel
authors.forename: U
authors.initials: U
authors.lastname: Zabel
authors.forename: K
authors.initials: K
authors.lastname: van Zee
authors.forename: J M
authors.initials: JM
authors.lastname: Müller
authors.forename: E
authors.initials: E
authors.lastname: Fanning
authors.forename: P A
authors.initials: PA
authors.lastname: Baeuerle
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D002522:Chlorocebus aethiops; D004268:DNA-Binding Proteins / Q000737:chemistry; D008958:Models, Molecular; D008969:Molecular Sequence Data; D015394:Molecular Structure; D016328:NF-kappa B / Q000737:chemistry* / Q000378:metabolism; D052002:NF-kappa B p50 Subunit; D009687:Nuclear Proteins / Q000737:chemistry; D011487:Protein Conformation; D011498:Protein Precursors / Q000737:chemistry* / Q000378:metabolism
chemical_list: D004268:DNA-Binding Proteins; D016328:NF-kappa B; D052002:NF-kappa B p50 Subunit; D009687:Nuclear Proteins; D011498:Protein Precursors