Inactivation of tumor suppressor Dlg1 augments transformation of a T-cell line induced by human T-cell leukemia virus type 1 Tax protein.

Abstract

BACKGROUND:

The interaction of human T-cell leukemia virus type 1 (HTLV-1) Tax1 protein with the tumor suppressor Dlg1 is correlated with cellular transformation.

RESULTS:

Here, we show that Dlg1 knockdown by RNA interference increases the ability of Tax1 to transform a mouse T-cell line (CTLL-2), as measured interleukin (IL)-2-independent growth. A Tax1 mutant defective for the Dlg1 interaction showed reduced transformation of CTLL-2 compared to wild type Tax1, but the transformation was minimally affected by Dlg1 reduction. The few Tax1DeltaC-transduced CTLL-2 cells that became transformed expressed less Dlg1 than parental cells, suggesting that Dlg1-low cells were selectively transformed by Tax1DeltaC. Moreover, all human T-cell lines immortalized by HTLV-1, including the recombinant HTLV-1-containing Tax1DeltaC, expressed less Dlg1 than control T-cell lines.

CONCLUSION:

These results suggest that inactivation of Dlg1 augments Tax1-mediated transformation of CTLL-2, and PDZ protein(s) other than Dlg1 are critically involved in the transformation.

• Authors: Kojiro Ishioka, Masaya Higuchi, Masahiko Takahashi, Sakiko Yoshida, Masayasu Oie, Yuetsu Tanaka, Sugata Takahashi, Li Xie, Patrick L Green, Masahiro Fujii
• Journal: Retrovirology (Retrovirology) Vol. 3 Pg. 71 (Oct 17 2006) ISSN: 1742-4690 [Electronic] England
• PMID: 17042961 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Discs Large Homolog 1 Protein
• Dlg1 protein, mouse
• Gene Products, tax
• Nerve Tissue Proteins
• SAP90-PSD95 Associated Proteins

Topics

• Animals
• Cell Line
• Cell Transformation, Viral (drug effects)
• Discs Large Homolog 1 Protein
• Gene Products, tax (metabolism, physiology)
• Gene Silencing
• Human T-lymphotropic virus 1 (physiology)
• Humans
• Jurkat Cells
• Mice
• Nerve Tissue Proteins (genetics, metabolism)
• SAP90-PSD95 Associated Proteins
• T-Lymphocytes (virology)