Differences in the ability of human T-cell lymphotropic virus type 1 (HTLV-1) and HTLV-2 tax to inhibit p53 function.
We have analyzed the functional activity of the p53 tumor suppressor in human T-cell lymphotropic virus type 2 (HTLV-2)-transformed cells. Abundant levels of the p53 protein were detected in both HTLV-2A and -2B virus-infected cell lines. The p53 was functionally inactive, however, both in transient-transfection assays using a p53 reporter plasmid and in induction of p53-responsive genes in response to gamma irradiation. We further investigated HTLV-2A Tax and HTLV-2B Tax effects on p53 activity. Interestingly, although Tax-2A and -2B inactivate p53, the Tax-2A protein appears to inhibit p53 function less efficiently than either Tax-1 or Tax-2B. In transient-cotransfection assays, Tax-1 and Tax-2B inactivated p53 by 80%, while Tax2A reduced p53 activity by 20%. In addition, Tax-2A does not increase the steady-state level of cellular p53 as well as Tax-1 or -2B does in the same assays. Cotransfection assays demonstrated that Tax-2A could efficiently transactivate CREB-responsive promoters to the same level as Tax-1 and Tax-2B, indicating that the protein was functional. This report provides evidence of the first functional difference between the HTLV-2A and -2B subtypes. This comparison of the action of HTLV-1 and HTLV-2 Tax proteins on p53 function will provide important insights into the mechanism of HTLV transformation.
Mahieux
R
R
Laboratory of Receptor Biology and Gene Expression,National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
Pise-Masison
C A
CA
Lambert
P F
PF
Nicot
C
C
De Marchis
L
L
Gessain
A
A
Green
P
P
Hall
W
W
Brady
J N
JN
D002461:Cell Line, Transformed; D002472:Cell Transformation, Viral; D005720:Gamma Rays; D005786:Gene Expression Regulation; D016356:Gene Products, tax / Q000235:genetics / Q000378:metabolism*; D015491:HTLV-II Infections / Q000821:virology; D015368:Human T-lymphotropic virus 1 / Q000235:genetics / Q000502:physiology*; D015367:Human T-lymphotropic virus 2 / Q000235:genetics / Q000502:physiology*; D006801:Humans; D019169:Jurkat Cells; D010766:Phosphorylation; D013601:T-Lymphocytes / Q000821:virology; D014158:Transcription, Genetic; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism* / Q000528:radiation effects
D016356:Gene Products, tax; D016159:Tumor Suppressor Protein p53