Regulation of NF-kappa B, AP-1, NFAT, and STAT1 nuclear import in T lymphocytes by noninvasive delivery of peptide carrying the nuclear localization sequence of NF-kappa B p50.

Torgerson TR, Colosia AD, Donahue JP, Lin YZ, Hawiger J
J Immunol. 1998 161 (11): 6084-92

PMID: 9834092

Activation of T lymphocytes by Ags or cytokines results in translocation of the transcription factors NF-kappa B, AP-1, NFAT, and STAT from the cytoplasm into the nucleus. The first step in the nuclear import process is recognition of a nuclear localization sequence (NLS) within the karyophilic protein by a cytoplasmic receptor such as the importin (karyopherin)-alpha subunit. The NLSs of NF-kappa B, AP-1, and NFAT differ and the NLS of STAT1 has not yet been identified. Herein we demonstrate that the inducible nuclear import of NF-kappa B, AP-1, NFAT, and STAT1 in Jurkat T lymphocytes is significantly inhibited by a cell-permeable peptide carrying the NLS of the NF-kappa B p50 subunit. NLS peptide-mediated disruption of the nuclear import of these transcription factors results in inhibition of I kappa B alpha and IL-2 gene expression, processes dependent on NF-kappa B or the combination of NF-kappa B, AP-1, and NFAT. Further, we show that inhibitory NLS peptide interacts in vitro with a cytoplasmic NLS receptor complex comprised of the Rch1/importin (karyopherin)-beta heterodimer expressed in Jurkat T cells. Taken together, these data indicate that the inducible nuclear import of NF-kappa B, AP-1, NFAT, and STAT1 in Jurkat T cells can be regulated by NLS peptide delivered noninvasively to the cytoplasm of Jurkat T cells to target members of the importin (karyopherin)-alpha beta NLS receptor complex.

MeSH Terms (26)

Amino Acid Sequence Biological Transport Cell Membrane Permeability Cell Nucleus Cytoplasm DNA-Binding Proteins Gene Expression Regulation, Neoplastic Humans I-kappa B Proteins Interleukin-2 Jurkat Cells Kinetics Molecular Sequence Data NF-kappa B NF-KappaB Inhibitor alpha NF-kappa B p50 Subunit NFATC Transcription Factors Nuclear Localization Signals Nuclear Proteins Peptides Signal Transduction STAT1 Transcription Factor T-Lymphocytes Trans-Activators Transcription Factor AP-1 Transcription Factors

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