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 G0/G1 cell cycle arrest. We have previously identified a classical biparti...

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Bibliographic Details
Published in:Biochemistry (Easton) 2002-12, Vol.41 (48), p.14306-14312
Main Authors: Wilson, Kevin C, Cruikshank, William W, Center, David M, Zhang, Yujun
Format: Article
Language:English
Subjects:
Active Transport, Cell Nucleus - genetics
Amino Acid Motifs - genetics
Amino Acid Motifs - physiology
Amino Acid Sequence
Animals
Casein Kinase II
CDC2 Protein Kinase - genetics
CDC2 Protein Kinase - metabolism
Cercopithecus aethiops
COS Cells
G1 Phase - genetics
Humans
Interleukin-16 - genetics
Interleukin-16 - physiology
Molecular Sequence Data
Mutagenesis, Site-Directed
Nuclear Localization Signals - genetics
Nuclear Localization Signals - metabolism
Nuclear Localization Signals - physiology
Peptide Fragments - genetics
Peptide Fragments - physiology
Phosphorylation
Protein Precursors - genetics
Protein Precursors - physiology
Protein Structure, Tertiary - genetics
Protein-Serine-Threonine Kinases - genetics
Protein-Serine-Threonine Kinases - metabolism
Resting Phase, Cell Cycle - genetics
Substrate Specificity - genetics
Transfection
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Summary: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 G0/G1 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 G0/G1 cell cycle arrest. This is the first description of a functional CcN motif in a cytokine precursor.
ISSN:0006-2960
1520-4995
DOI:10.1021/bi020163v