Binding of HTLV-1 tax oncoprotein to the precursor of interleukin-16, a T cell PDZ domain-containing protein.
HTLV-1 Tax oncoprotein interacts with various cellular factors and modulates transcription and the cell cycle. In that role it is sufficient to create T cell malignancies in the absence of HTLV-1 infection. HTLV-1 Tax protein has been reported to bind to cellular proteins containing PDZ domains in vitro. The precursor of human interleukin 16, pro-IL-16, is an abundant cellular protein present in human peripheral blood T cells. Pro-IL-16 contains three PDZ domains. It has been shown that expression of pro-IL-16 in pro-IL-16 negative cells induces a G(0)/G(1) arrest in the cell cycle. The current studies demonstrate that Tax binds to pro-IL-16 in HTLV-1 infected human T cells. We mapped the Tax binding site to the first PDZ domain of pro-IL-16. Over-expression of Tax in COS cells resulted in fewer cells in G(0)/G(1) consistent with its activity to induce G(1)- to S-phase progression in lymphocytes, while over-expression of pro-IL-16 in COS cells resulted in G(0)/G(1) arrest. Co-expression of wild type Tax with pro-IL-16 in COS cells negated the effects of pro-IL-16, an effect not observed with Tax mutated at its PDZ binding C-terminus. These results suggest that one of the effects of Tax on growth deregulation in HTLV-1 infected T cells might be mediated by its binding to pro-IL-16.
Wilson
Kevin C
KC
The Pulmonary Center and Department of Medicine, Boston University School of Medicine, Boston, MA 02118, USA.
Center
David M
DM
Cruikshank
William W
WW
Zhang
Yujun
Y
D048868:Adaptor Proteins, Signal Transducing; D000595:Amino Acid Sequence; D000818:Animals; D019556:COS Cells; D002453:Cell Cycle; D002460:Cell Line; D000074288:Discs Large Homolog 1 Protein; D016356:Gene Products, tax / Q000378:metabolism*; D016147:Genes, Tumor Suppressor; D015368:Human T-lymphotropic virus 1 / Q000378:metabolism*; D006801:Humans; D019410:Interleukin-16 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008565:Membrane Proteins; D008969:Molecular Sequence Data; D011498:Protein Precursors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011506:Proteins / Q000737:chemistry / Q000235:genetics; D013601:T-Lymphocytes / Q000378:metabolism / Q000821:virology*
D048868:Adaptor Proteins, Signal Transducing; C513314:DLG1 protein, human; D000074288:Discs Large Homolog 1 Protein; D016356:Gene Products, tax; D019410:Interleukin-16; D008565:Membrane Proteins; D011498:Protein Precursors; D011506:Proteins