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Nuclear translocation of the N-terminal prodomain of interleukin-16

Y Zhang1, H Kornfeld, W W Cruikshank

  • 1Pulmonary Center, Boston University School of Medicine, Boston, Massachusetts 02118, USA. yzhang@bupula.bu.edu

The Journal of Biological Chemistry
|October 18, 2000
PubMed

Insights

The N-terminal prodomain of Interleukin-16 (IL-16) moves to the nucleus after cleavage. This nuclear targeting of the IL-16 prodomain halts cell cycle progression, suggesting a dual function for the precursor protein.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Immunology

Background:

  • Interleukin-16 (IL-16) is a cytokine with known roles in T cell activation and HIV replication.
  • Its functions are attributed to a mature C-terminal peptide derived from the precursor pro-IL-16.
  • The biological role of the N-terminal prodomain of pro-IL-16 remains largely uncharacterized.

Purpose of the Study:

  • To investigate the cellular localization and biological function of the N-terminal prodomain of pro-IL-16.
  • To determine if the prodomain has any role beyond being a precursor to mature IL-16.
  • To elucidate the functional significance of the conserved N-terminal prodomain.

Main Methods:

  • Analysis of pro-IL-16 processing and cleavage by caspase-3.
  • Identification and characterization of the nuclear localization signal within the prodomain.
  • Cell cycle analysis to assess the impact of prodomain nuclear translocation.

Main Results:

  • The N-terminal prodomain of pro-IL-16 translocates into the nucleus following cleavage of the C-terminal mature IL-16.
  • A classical bipartite nuclear targeting motif was identified in the prodomain.
  • Nuclear localization of the IL-16 prodomain induces a G(0)/G(1) arrest in the cell cycle.

Conclusions:

  • Pro-IL-16 is cleaved into two functional proteins: a secreted cytokine and an N-terminal nuclear factor.
  • The N-terminal prodomain plays a critical role in regulating cell cycle progression.
  • The conserved nature and dual function suggest significant biological importance for the prodomain.

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