Distinct nuclear body components, PML and SMRT, regulate the trans-acting function of HTLV-1 Tax oncoprotein.
Several viruses target cellular promyelocytic leukemia (PML)-nuclear bodies (PML-NBs) to induce their disruption, marked morphological changes in these structures or the relocation to PML-NB components to the cytoplasm of infected cells. PML conversely interferes with viral replication. We demonstrate that PML acts as a coactivator for the human T-cell leukemia virus type 1 (HTLV-1) Tax oncoprotein without direct binding. Tax was identified within interchromatin granule clusters (IGCs)/RNA splicing bodies (SBs), not PML-NBs; Tax expression did not affect PML-NB formation. Moreover, PML and CBP/p300 cooperatively activated Tax-mediated HTLV-1-LTR-dependent gene expression. Interestingly, two PML mutants, PML-RAR and PMLDelta216-331, which fail to form PML-NBs, could also coactivate Tax-mediated trans-acting function but had no effect on retinoic acid receptor (RAR)- or p53-dependent gene expression. In contrast, SMRT (silencing mediator for retinoic acid and thyroid hormone receptors), a nuclear corepressor found within the matrix-associated deacetylase (MAD) nuclear body, relocalized into Tax-associated nuclear bodies upon coexpression with Tax. SMRT coactivated the trans-acting function of Tax through direct binding. Coexpression of SMRT and PML resulted in an additive activation of Tax trans-acting function. Thus, crosstalk between distinct nuclear bodies may control Tax function.
Ariumi
Yasuo
Y
Laboratory of Human Tumor Viruses, Institute for Virus Research, Kyoto University, Sakyo-ku, Kyoto 606-8507, Japan.
Ego
Takeshi
T
Kaida
Atsushi
A
Matsumoto
Mikiko
M
Pandolfi
Pier Paolo
PP
Shimotohno
Kunitada
K
D001483:Base Sequence; D015153:Blotting, Western; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism*; D017931:DNA Primers; D004268:DNA-Binding Proteins / Q000502:physiology*; D005455:Fluorescent Antibody Technique; D016356:Gene Products, tax / Q000502:physiology*; D006801:Humans; D009363:Neoplasm Proteins / Q000502:physiology*; D009687:Nuclear Proteins; D056985:Nuclear Receptor Co-Repressor 2; D011233:Precipitin Tests; D000071156:Promyelocytic Leukemia Protein; D012097:Repressor Proteins / Q000502:physiology*; D015534:Trans-Activators / Q000502:physiology*; D014157:Transcription Factors / Q000502:physiology*; D025521:Tumor Suppressor Proteins
D017931:DNA Primers; D004268:DNA-Binding Proteins; D016356:Gene Products, tax; C539130:NCOR2 protein, human; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D056985:Nuclear Receptor Co-Repressor 2; D000071156:Promyelocytic Leukemia Protein; D012097:Repressor Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; C070576:PML protein, human