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

Ishioka K, Higuchi M, Takahashi M, Yoshida S, Oie M, Tanaka Y, Takahashi S, Xie L, Green PL, Fujii M - Retrovirology (2006)

Bottom Line: 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.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.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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Division of Virology, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi-Dori, Niigata, Japan. kojiro1@med.niigata-u.ac.jp

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.

Show MeSH

Related in: MedlinePlus

Dlg1 expression is lower in HTLV-1-transformed human T-cell lines than HTLV-1 negative cell lines. Cell lysates were prepared from seven HTLV-1 transformed T-cell lines (lanes 1–7) and three HTLV-1 negative T-cell lines (lanes 8–10). The expression of hDlg1 (top), Syntrophin β (second column), Tax1 (third column), or Tubulin (bottom) was measured by Western blot analysis using corresponding antibodies.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC1622753&req=5

Figure 6: Dlg1 expression is lower in HTLV-1-transformed human T-cell lines than HTLV-1 negative cell lines. Cell lysates were prepared from seven HTLV-1 transformed T-cell lines (lanes 1–7) and three HTLV-1 negative T-cell lines (lanes 8–10). The expression of hDlg1 (top), Syntrophin β (second column), Tax1 (third column), or Tubulin (bottom) was measured by Western blot analysis using corresponding antibodies.

Mentions: We also examined the expression of Dlg1 protein in HTLV-1-transformed T-cell lines (Figure 6). All seven HTLV-1-transformed T-cell lines, including one transformed by HTLV-1ΔPBM with a deletion of the Tax1 PBM, expressed lower amounts of Dlg1 than three HTLV-1 negative human T-cell lines. These results suggest that the Dlg1-low phenotype is preferential for HTLV-1-mediated transformation of human T-cells. The molecular weight of Dlg1 in three HTLV-1-infected T-cell lines (ILT-Koy, SLB-1, HUT-102) that express high amounts of Tax1 was greater than that in HTLV-1 negative T-cell lines, which corresponds to the phosphorylation of Dlg1 in HTLV-1-infected T-cell lines [28]. The biological relevance of phosphorylated Dlg1 in HTLV-1-transformed cells is unclear [25].


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

Ishioka K, Higuchi M, Takahashi M, Yoshida S, Oie M, Tanaka Y, Takahashi S, Xie L, Green PL, Fujii M - Retrovirology (2006)

Dlg1 expression is lower in HTLV-1-transformed human T-cell lines than HTLV-1 negative cell lines. Cell lysates were prepared from seven HTLV-1 transformed T-cell lines (lanes 1–7) and three HTLV-1 negative T-cell lines (lanes 8–10). The expression of hDlg1 (top), Syntrophin β (second column), Tax1 (third column), or Tubulin (bottom) was measured by Western blot analysis using corresponding antibodies.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC1622753&req=5

Figure 6: Dlg1 expression is lower in HTLV-1-transformed human T-cell lines than HTLV-1 negative cell lines. Cell lysates were prepared from seven HTLV-1 transformed T-cell lines (lanes 1–7) and three HTLV-1 negative T-cell lines (lanes 8–10). The expression of hDlg1 (top), Syntrophin β (second column), Tax1 (third column), or Tubulin (bottom) was measured by Western blot analysis using corresponding antibodies.
Mentions: We also examined the expression of Dlg1 protein in HTLV-1-transformed T-cell lines (Figure 6). All seven HTLV-1-transformed T-cell lines, including one transformed by HTLV-1ΔPBM with a deletion of the Tax1 PBM, expressed lower amounts of Dlg1 than three HTLV-1 negative human T-cell lines. These results suggest that the Dlg1-low phenotype is preferential for HTLV-1-mediated transformation of human T-cells. The molecular weight of Dlg1 in three HTLV-1-infected T-cell lines (ILT-Koy, SLB-1, HUT-102) that express high amounts of Tax1 was greater than that in HTLV-1 negative T-cell lines, which corresponds to the phosphorylation of Dlg1 in HTLV-1-infected T-cell lines [28]. The biological relevance of phosphorylated Dlg1 in HTLV-1-transformed cells is unclear [25].

Bottom Line: 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.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.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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Division of Virology, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi-Dori, Niigata, Japan. kojiro1@med.niigata-u.ac.jp

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.

Show MeSH
Related in: MedlinePlus