SEARCH:   Advanced

Blood, 1 February 2007, Vol. 109, No. 3, pp. 1211-1219. Prepublished online as a Blood First Edition Paper on October 3, 2006; DOI 10.1182/blood-2005-12-040972. This Article Full Text Full Text (PDF) Supplemental Figures All Versions of this Article: blood-2005-12-040972v1 109/3/1211    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 Yoshida, C. Articles by Melo, J. V. Search for Related Content PubMed PubMed Citation Articles by Yoshida, C. Articles by Melo, J. V. Related Collections Neoplasia Oncogenes and Tumor Suppressors Signal Transduction Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  NEOPLASIA Bcr-Abl signaling through the PI-3/S6 kinase pathway inhibits nuclear translocation of the transcription factor Bach2, which represses the antiapoptotic factor heme oxygenase-1 Chikashi Yoshida1, Fumiko Yoshida1, Daniel E. Sears1, Stephen M. Hart1, Dai Ikebe2, Akihiko Muto3, Subham Basu4, Kazuhiko Igarashi3, and Junia V. Melo1 1 Department of Haematology, Imperial College London, Hammersmith Hospital, United Kingdom; 2 Institute of Basic Medical Sciences, University of Tsukuba, Japan; 3 Department of Biochemistry, Tohoku University School of Medicine, Sendai, Japan; 4 Cell Survival Signalling Laboratory, Cancer Research UK Molecular Oncology Unit, Barts, and The London School of Medicine and Dentistry, London, United Kingdom The malignant phenotype of chronic myeloid leukemia (CML) is due to the abnormal tyrosine kinase activity of the Bcr-Abl oncoprotein. We have previously reported that expression of the Bach2 transcription factor, which induces apoptosis in response to oxidative stress, is greatly reduced in CML cells. Because these cells are resistant to apoptosis, we tested whether Bach2 could also be regulated through posttranslational mechanisms that promote inhibition of the apoptotic response to mutagenic stimuli in CML. We found that Bach2 is phosphorylated on S521 via the phosphatidylinositol-3/S6 kinase pathway, and substitution of this site to alanine leads to nuclear accumulation of the protein, indicating that this phosphorylation is important for its subcellular localization. Ectopic expression of the S521 mutant imparts greater impairment to CML cell growth than the wild-type factor. Furthermore, we showed that Bach2 transcriptionally represses heme oxygenase-1, an antiapoptotic factor up-regulated in CML. Because CML cells are known to produce high levels of intracellular reactive oxygen species, overexpression of heme oxygenase-1 resulting from inhibition of Bach2 activity may contribute to their genomic instability and leukemic phenotype. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: M. Mayerhofer, K. V. Gleixner, J. Mayerhofer, G. Hoermann, E. Jaeger, K. J. Aichberger, R. G. Ott, K. Greish, H. Nakamura, S. Derdak, et al. Targeting of heat shock protein 32 (Hsp32)/heme oxygenase-1 (HO-1) in leukemic cells in chronic myeloid leukemia: a novel approach to overcome resistance against imatinib Blood, February 15, 2008; 111(4): 2200 - 2210. [Abstract] [Full Text] [PDF] K. Igarashi, K. Ochiai, and A. Muto Architecture and Dynamics of the Transcription Factor Network that Regulates B-to-Plasma Cell Differentiation J. Biochem., June 1, 2007; 141(6): 783 - 789. [Abstract] [Full Text] [PDF] R. Blum, R. Elkon, S. Yaari, A. Zundelevich, J. Jacob-Hirsch, G. Rechavi, R. Shamir, and Y. Kloog Gene Expression Signature of Human Cancer Cell Lines Treated with the Ras Inhibitor Salirasib (S-Farnesylthiosalicylic Acid) Cancer Res., April 1, 2007; 67(7): 3320 - 3328. [Abstract] [Full Text] [PDF]

	Copyright © 2007 by American Society of Hematology         Online ISSN: 1528-0020