Distinct nuclear body components, PML and SMRT, regulate the trans-acting function of HTLV-1 tax oncoprotein Journal Article

  

Authors:	Ariumi, Y.; Ego, T.; Kaida, A.; Matsumoto, M.; Pandolfi, P. P.; Shimotohno, K.
Article Title:	Distinct nuclear body components, PML and SMRT, regulate the trans-acting function of HTLV-1 tax oncoprotein
Abstract:	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 I (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, relocatized 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.
Keywords:	tumor suppression; acute promyelocytic leukemia; pml; bodies; cbp; rar-alpha; nuclear body; htlv-1; tax; smrt; cell leukemia-virus; creb binding-protein; replication compartments; viral transactivator; coactivator cbp; type-1 tax
Journal Title:	Oncogene
Volume:	22
Issue:	11
ISSN:	0950-9232
Publisher:	Nature Publishing Group
Date Published:	2003-03-20
Start Page:	1611
End Page:	1619
Language:	English
ACCESSION:	WOS:000181580500003
DOI:	10.1038/sj.onc.1206244
PROVIDER:	wos
PUBMED:	12642864
Notes:	Article -- Source: Wos

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