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Blood, 1 July 2007, Vol. 110, No. 1, pp. 305-312. Prepublished online as a Blood First Edition Paper on March 20, 2007; DOI 10.1182/blood-2006-07-033209. This Article Full Text Full Text (PDF) Supplemental Figures All Versions of this Article: blood-2006-07-033209v1 110/1/305    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 HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Yan, M. Articles by Zhang, D.-E. Search for Related Content PubMed PubMed Citation Articles by Yan, M. Articles by Zhang, D.-E. Related Collections Immunobiology Neoplasia Oncogenes and Tumor Suppressors Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  NEOPLASIA Ubp43 regulates BCR-ABL leukemogenesis via the type 1 interferon receptor signaling Ming Yan1, Jiann-Kae Luo1, Kenneth J. Ritchie1, Ikuya Sakai2, Kasuto Takeuchi2, Ruibao Ren3, and Dong-Er Zhang1 1 Division of Oncovirology, Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA; 2 First Department of Internal Medicine, Ehime University School of Medicine, Shigenobu, Ehime, Japan; 3 Rosenstiel Basic Medical Sciences Research Center, Department of Biology, Brandeis University, Waltham, MA Interferon (IFN) signaling induces the expression of interferon-responsive genes and leads to the activation of pathways that are involved in the innate immune response. Ubp43 is an ISG15-specific isopeptidase, the expression of which is activated by IFN. Ubp43 knock-out mice are hypersensitive to IFN-/ß and have enhanced resistance to lethal viral and bacterial infections. Here we show that in addition to protection against foreign pathogens, Ubp43 deficiency increases the resistance to oncogenic transformation by BCR-ABL. BCR-ABL viral transduction/transplantation of wild-type bone marrow cells results in the rapid development of a chronic myeloid leukemia (CML)–like myeloproliferative disease; in contrast, a significantly increased latency of disease development is observed following BCR-ABL viral transduction/transplantation of Ubp43-deficient bone marrow cells. This resistance to leukemic development is dependent on type 1 IFN (IFN-/ß) signaling in Ubp43-deficient cells. Increased levels of type 1 IFN are also detected in the serum of CML mice. These results suggest that inhibition of Ubp43-negative effect on IFN signaling can potentiate the response to increased endogenous IFN levels in innate immune responses against cancer development, indicating that pharmacological inhibition of Ubp43 may be of benefit in cancers and others diseases in which interferon is currently prescribed. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: E. Katsoulidis, A. Sassano, B. Majchrzak-Kita, N. Carayol, P. Yoon, A. Jordan, B. J. Druker, E. N. Fish, and L. C. Platanias Suppression of Interferon (IFN)-inducible Genes and IFN-mediated Functional Responses in BCR-ABL-expressing Cells J. Biol. Chem., April 18, 2008; 283(16): 10793 - 10803. [Abstract] [Full Text] [PDF]

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