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


CONCLUSIONS
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.
Ishioka
Kojiro
K
Division of Virology, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi-Dori, Niigata, Japan. kojiro1@med.niigata-u.ac.jp
Higuchi
Masaya
M
Takahashi
Masahiko
M
Yoshida
Sakiko
S
Oie
Masayasu
M
Tanaka
Yuetsu
Y
Takahashi
Sugata
S
Xie
Li
L
Green
Patrick L
PL
Fujii
Masahiro
M
D000818:Animals; D002460:Cell Line; D002472:Cell Transformation, Viral / Q000187:drug effects*; D000074288:Discs Large Homolog 1 Protein; D016356:Gene Products, tax / Q000378:metabolism / Q000502:physiology*; D020868:Gene Silencing; D015368:Human T-lymphotropic virus 1 / Q000502:physiology; D006801:Humans; D019169:Jurkat Cells; D051379:Mice; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism; D000074407:SAP90-PSD95 Associated Proteins; D013601:T-Lymphocytes / Q000821:virology
D000074288:Discs Large Homolog 1 Protein; C000614189:Dlg1 protein, mouse; D016356:Gene Products, tax; D009419:Nerve Tissue Proteins; D000074407:SAP90-PSD95 Associated Proteins