Inactivation of p53 by HTLV type 1 and HTLV type 2 Tax trans-activators.
Human T cell lymphotropic virus type II (HTLV-2) was originally isolated from a patient with a hairy T cell leukemia. It has been associated with rare cases of CD8(+) T lymphoproliferative disorders, and has a controversial role as a pathogen. The loss of p53 function, as a consequence of mutation or inactivation, increases the chances of genetic damage. Indeed, the importance of p53 as a tumor suppressor is evident from the fact that over 60% of all human cancers have a mutant or inactive p53. p53 status has been extensively studied in HTLV-1-infected cell lines. Interestingly, despite the fact that p53 mutations have been found in only a minority of cells, the p53 functions were found to be impaired. We have analyzed the functional activity of the p53 tumor suppressor in cells transformed with HTLV-2 subtypes A and B. As with HTLV-1-infected cells, abundant levels of the p53 protein are detected in HTLV-2 virus-infected cell lines. Using p53 reporter plasmid or induction of p53-responsive genes in response to gamma-irradiation, the p53 was found to be transcriptionally inhibited in HTLV-2-infected cells. 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 T cells, but not in fibroblasts.
Mahieux
R
R
Basic Research Laboratory, Bldg. 41, NCI, NIH, Bethesda, Maryland 20892, USA.
Pise-Masison
C A
CA
Nicot
C
C
Green
P
P
Hall
W W
WW
Brady
J N
JN
D000818:Animals; D002461:Cell Line, Transformed; D016356:Gene Products, tax / Q000378:metabolism*; D015490:HTLV-I Infections / Q000821:virology; D015491:HTLV-II Infections / Q000821:virology; D015368:Human T-lymphotropic virus 1 / Q000502:physiology*; D015367:Human T-lymphotropic virus 2 / Q000502:physiology*; D006801:Humans; D051379:Mice; D013601:T-Lymphocytes / Q000821:virology; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D016159:Tumor Suppressor Protein p53 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism*
D016356:Gene Products, tax; D016159:Tumor Suppressor Protein p53