Functional impairment of p73 and p51, the p53-related proteins, by the human T-cell leukemia virus type 1 Tax oncoprotein.
We have previously demonstrated that the human T-cell leukemia virus type 1 (HTLV-1) Tax oncoprotein represses the trans-activation function of p53 tumor suppressor protein. Recently, several proteins with sequence homology to p53 have been identified. In this study, we demonstrated that Tax represses the trans-activation functions of p73alpha, p73beta, and p51A, the p53-related proteins, as well as p53. Moreover, a mutant Tax of coactivator CBP-binding site (K88A), which activated NF-kappaB but not CREB pathway, could not repress the p73 nor p51 trans-activation functions, indicating that CBP-binding domain of Tax is essential for the suppression of their functions. Using proteins of Gal4-fused N-terminal region of p73 and p51, we showed that Tax-mediated inactivation of p73 or p51 requires for their N-terminal trans-activation domains. Furthermore, only the putative N-terminal trans-activation domains of them did not have enough transcriptional activities and their adjacent regions are essential for their full trans-activation, suggesting the existence of their second trans-activation subdomains. Thus, HTLV-1 Tax inactivated the p53-related proteins through their N-terminal trans-activation domains.
Kaida
A
A
Department of Viral Oncology, Institute for Virus Research, Kyoto University, Japan.
Ariumi
Y
Y
Ueda
Y
Y
Lin
J Y
JY
Hijikata
M
M
Ikawa
S
S
Shimotohno
K
K
D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry; D015967:Gene Expression Regulation, Viral; D016356:Gene Products, tax / Q000502:physiology*; D016147:Genes, Tumor Suppressor; D016355:Genes, pX; D015368:Human T-lymphotropic virus 1 / Q000235:genetics / Q000502:physiology*; D006801:Humans; D009687:Nuclear Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry; D010750:Phosphoproteins; D017434:Protein Structure, Tertiary; D011993:Recombinant Fusion Proteins / Q000502:physiology; D013329:Structure-Activity Relationship; D013601:T-Lymphocytes / Q000166:cytology / Q000821:virology; D015534:Trans-Activators; D014157:Transcription Factors; D015533:Transcriptional Activation / Q000502:physiology*; D014162:Transfection; D000072160:Tumor Protein p73; D025521:Tumor Suppressor Proteins
D004268:DNA-Binding Proteins; D016356:Gene Products, tax; D009687:Nuclear Proteins; D010750:Phosphoproteins; D011993:Recombinant Fusion Proteins; C115051:TP63 protein, human; C000606460:TP73 protein, human; D015534:Trans-Activators; D014157:Transcription Factors; D000072160:Tumor Protein p73; D025521:Tumor Suppressor Proteins