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Blood, 30 April 2009, Vol. 113, No. 18, pp. 4370-4380. Prepublished online as a Blood First Edition Paper on January 8, 2009; DOI 10.1182/blood-2008-10-185660. This Article Full Text Full Text (PDF) Supplemental Figures All Versions of this Article: blood-2008-10-185660v1 113/18/4370    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Yan, P. Articles by Xiao, G. Search for Related Content PubMed PubMed Citation Articles by Yan, P. Articles by Xiao, G. Related Collections Lymphoid Neoplasia Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  LYMPHOID NEOPLASIA PDLIM2 suppresses human T-cell leukemia virus type I Tax-mediated tumorigenesis by targeting Tax into the nuclear matrix for proteasomal degradation Pengrong Yan1,2,*, Jing Fu1,2,*, Zhaoxia Qu1,2, Shirong Li1,2, Takashi Tanaka3, Michael J. Grusby4, and Gutian Xiao1,2 1 University of Pittsburgh Cancer Institute, University of Pittsburgh Medical Center, PA; 2 Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, PA; 3 Laboratory for Host Defense, RIKEN Research Center for Allergy and Immunology, Yokohama, Japan; and 4 Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, MA The mechanisms by which the human T-cell leukemia virus type I (HTLV-I) Tax oncoprotein deregulates cellular signaling for oncogenesis have been extensively studied, but how Tax itself is regulated remains largely unknown. Here we report that Tax was negatively regulated by PDLIM2, which promoted Tax K48-linked polyubiquitination. In addition, PDLIM2 recruited Tax from its functional sites into the nuclear matrix where the polyubiquitinated Tax was degraded by the proteasome. Consistently, PDLIM2 suppressed Tax-mediated signaling activation, cell transformation, and oncogenesis both in vitro and in animal. Notably, PDLIM2 expression was down-regulated in HTLV-I–transformed T cells, and PDLIM2 reconstitution reversed the tumorigenicity of the malignant cells. These studies indicate that the counterbalance between HTLV-I/Tax and PDLIM2 may determine the outcome of HTLV-I infection. These studies also suggest a potential therapeutic strategy for cancers and other diseases associated with HTLV-I infection and/or PDLIM2 deregulation. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

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