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Blood, 15 January 2007, Vol. 109, No. 2, pp. 763-768. Prepublished online as a Blood First Edition Paper on September 14, 2006; DOI 10.1182/blood-2006-05-024752. This Article Full Text Full Text (PDF) Supplemental Table and Figure All Versions of this Article: blood-2006-05-024752v1 109/2/763    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 Wahlstrom, A. M. Articles by Bergo, M. O. Search for Related Content PubMed PubMed Citation Articles by Wahlstrom, A. M. Articles by Bergo, M. O. Related Collections Neoplasia Oncogenes and Tumor Suppressors Signal Transduction Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  NEOPLASIA Rce1 deficiency accelerates the development of K-RAS–induced myeloproliferative disease Annika M. Wahlstrom1, Briony A. Cutts1, Christin Karlsson1, Karin M. E. Andersson1, Meng Liu1,2, Anna-Karin M. Sjogren1, Birgitta Swolin3, Stephen G. Young4, and Martin O. Bergo1, 1 Wallenberg Laboratory, Department of Medicine, and 3 Department of Clinical Chemistry and Transfusion Medicine, Sahlgrenska University Hospital, Gothenburg, Sweden; 2 Department of Neurosurgery, Qilu Hospital, Shandong University, Jinan, China; 4 Department of Internal Medicine, David Geffen School of Medicine, University of California–Los Angeles The RAS proteins undergo farnesylation of a carboxyl-terminal cysteine (the "C" of the carboxyl-terminal CaaX motif). After farnesylation, the 3 amino acids downstream from the farnesyl cysteine (the -aaX of the CaaX motif) are released by RAS-converting enzyme 1 (RCE1). We previously showed that inactivation of Rce1 in mouse fibroblasts mislocalizes RAS proteins away from the plasma membrane and inhibits RAS transformation. Therefore, we hypothesized that the inactivation of Rce1 might inhibit RAS transformation in vivo. To test this hypothesis, we used Cre/loxP recombination techniques to simultaneously inactivate Rce1 and activate a latent oncogenic K-RAS allele in hematopoietic cells in mice. Normally, activation of the oncogenic K-RAS allele in hematopoietic cells leads to rapidly progressing and lethal myeloproliferative disease. Contrary to our hypothesis, the inactivation of Rce1 actually increased peripheral leukocytosis, increased the release of immature hematopoietic cells into the circulation and the infiltration of cells into liver and spleen, and caused mice to die more rapidly. Moreover, in the absence of Rce1, splenocytes and bone marrow cells expressing oncogenic K-RAS yielded more and larger colonies when grown in methylcellulose. We conclude that the inactivation of Rce1 worsens the myeloproliferative disease caused by oncogenic K-RAS. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: A. M. Wahlstrom, B. A. Cutts, M. Liu, A. Lindskog, C. Karlsson, A.-K. M. Sjogren, K. M. E. Andersson, S. G. Young, and M. O. Bergo Inactivating Icmt ameliorates K-RAS-induced myeloproliferative disease Blood, August 15, 2008; 112(4): 1357 - 1365. [Abstract] [Full Text] [PDF]

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