Prointerleukin-16 contains a functional CcN motif that regulates nuclear localization.
The immunomodulatory cytokine interleukin-16 (IL-16) represents the secreted C-terminus of a larger precursor, pro-IL-16. Following cleavage by caspase 3, the residual N-terminal domain translocates into the nucleus, inducing G(0)/G(1) cell cycle arrest. We have previously identified a classical bipartite nuclear localization sequence (NLS) in the N-terminal domain of pro-IL-16. We ... now show that N-terminal to the NLS domain of pro-IL-16 are protein kinase CK2 substrate and cdc2 kinase substrate sites which, along with the NLS, constitute a dual phosphorylation-regulated CcN motif which regulates nuclear localization of pro-IL-16. In addition, we demonstrate that mutation of either site is associated with impairment of the N-terminal domain's ability to induce G(0)/G(1) cell cycle arrest. This is the first description of a functional CcN motif in a cytokine precursor.
Mesh Terms:
Active Transport, Cell Nucleus, Amino Acid Motifs, Amino Acid Sequence, Animals, CDC2 Protein Kinase, COS Cells, Casein Kinase II, Cercopithecus aethiops, G0 Phase, G1 Phase, Humans, Interleukin-16, Molecular Sequence Data, Mutagenesis, Site-Directed, Nuclear Localization Signals, Peptide Fragments, Phosphorylation, Protein Precursors, Protein Structure, Tertiary, Protein-Serine-Threonine Kinases, Substrate Specificity, Transfection
Active Transport, Cell Nucleus, Amino Acid Motifs, Amino Acid Sequence, Animals, CDC2 Protein Kinase, COS Cells, Casein Kinase II, Cercopithecus aethiops, G0 Phase, G1 Phase, Humans, Interleukin-16, Molecular Sequence Data, Mutagenesis, Site-Directed, Nuclear Localization Signals, Peptide Fragments, Phosphorylation, Protein Precursors, Protein Structure, Tertiary, Protein-Serine-Threonine Kinases, Substrate Specificity, Transfection
Biochemistry
Date: Dec. 03, 2002
PubMed ID: 12450396
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