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Blood, 1 September 2004, Vol. 104, No. 5, pp. 1314-1323. Prepublished online as a Blood First Edition Paper on May 13, 2004; DOI 10.1182/blood-2004-01-0046. This Article Full Text (PDF) All Versions of this Article: 2004-01-0046v1 104/5/1314    most recent Alert me when this article is cited Alert me if a correction is posted 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 Harris, M. N Articles by Chen, X. Search for Related Content PubMed PubMed Citation Articles by Harris, M. N Articles by Chen, X. Related Collections Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted January 7, 2004 Accepted April 28, 2004 Comparative Proteomic Analysis of All-trans-Retinoic Acid Treatment Reveals Systematic Post-Transcriptional Control Mechanisms in Acute Promyelocytic Leukemia Michael N Harris, Bulent Ozpolat, Fadi Abdi, Sheng Gu, Allison Legler, Kwasi E Muwuenyega, Maribel Tirado-Gomez, Gabriel Lopez-Berestein, and Xian Chen* BN-2, Biosciences Division, Los Alamos National Laboratory, Los Alamos, NM, USA Bioimmunotherapy, MD Anderson Cancer Center, Houston, TX, USA Applied Biosystems, Framingham, MA, USA * Corresponding author; email: chen_xian{at}lanl.gov. All-trans-retinoic acid (ATRA) induces growth inhibition, differentiation, and apoptosis in cancer cells including acute promyelocytic leukemia (APL). In APL, expression of PML-RAR fusion protein due to the t(15;17) reciprocal translocation leads to a block in the promyelocytic stage of differentiation. We studied here molecular mechanisms involved in ATRA-induced growth inhibition and myeloid cell differentiation in APL. By employing comprehensive high-throughput proteomic methods of 2-D gel electrophoresis and amino acid coded mass tagging coupled with ESI mass spectrometry, we systematically identified a total of 59 differentially expressed proteins that were consistently modulated in response to ATRA-treatment. The data revealed significant downregulation of eukaryotic initiation and elongation factors, IF2, eIF4AI, eIF4G, eIF5, eIF6, eEF1A-1, EF-1-, eEF1, 14-3-3, and 14-3-3/ (p<0.05). The translational inhibitor DAP5/p97/NAT1 and PML isoform-1 were found upregulated (p<0.05). Additionally, the downregulation of hnRNP C1/C2, UP2, K, F, snRNP D3, E, nucleoprotein TPR, and PP2A were found (p<0.05) and function in pre-mRNA processing, splicing, and export events. Importantly, these proteomic findings were validated by western blot analysis. Our data in comparison to previous cDNA microarray studies and our RT-PCR experiments demonstrate that broad networks of post-transcriptional suppressive pathways are activated during ATRA-induced growth inhibition processes in APL. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Posttranscriptional regulation of posttranscriptional regulators Steve Collins Blood 2004 104: 1234-1235. [Full Text] [PDF] This article has been cited by other articles: J. Zhang, L.-P. Song, Y. Huang, Q. Zhao, K.-W. Zhao, and G.-Q. Chen Accumulation of hypoxia-inducible factor-1{alpha} protein and its role in the differentiation of myeloid leukemic cells induced by all-trans retinoic acid Haematologica, October 1, 2008; 93(10): 1480 - 1487. [Abstract] [Full Text] [PDF] A. J. K. Williamson, D. L. Smith, D. Blinco, R. D. Unwin, S. Pearson, C. Wilson, C. Miller, L. Lancashire, G. Lacaud, V. Kouskoff, et al. Quantitative Proteomics Analysis Demonstrates Post-transcriptional Regulation of Embryonic Stem Cell Differentiation to Hematopoiesis Mol. Cell. Proteomics, March 1, 2008; 7(3): 459 - 472. [Abstract] [Full Text] [PDF] H. Hattori, X. Zhang, Y. Jia, K. K. Subramanian, H. Jo, F. Loison, P. E. Newburger, and H. R. Luo RNAi screen identifies UBE2D3 as a mediator of all-trans retinoic acid-induced cell growth arrest in human acute promyelocytic NB4 cells Blood, July 15, 2007; 110(2): 640 - 650. [Abstract] [Full Text] [PDF] B. Ozpolat, U. Akar, M. Steiner, I. Zorrilla-Calancha, M. Tirado-Gomez, N. Colburn, M. Danilenko, S. Kornblau, and G. Lopez Berestein Programmed Cell Death-4 Tumor Suppressor Protein Contributes to Retinoic Acid-Induced Terminal Granulocytic Differentiation of Human Myeloid Leukemia Cells Mol. Cancer Res., January 1, 2007; 5(1): 95 - 108. [Abstract] [Full Text] [PDF] A. Borriello, V. Cucciolla, M. Criscuolo, S. Indaco, A. Oliva, A. Giovane, D. Bencivenga, A. Iolascon, V. Zappia, and F. Della Ragione Retinoic Acid Induces p27Kip1 Nuclear Accumulation by Modulating Its Phosphorylation. Cancer Res., April 15, 2006; 66(8): 4240 - 4248. [Abstract] [Full Text] [PDF] M. Notari, P. Neviani, R. Santhanam, B. W. Blaser, J.-S. Chang, A. Galietta, A. E. Willis, D. C. Roy, M. A. Caligiuri, G. Marcucci, et al. A MAPK/HNRPK pathway controls BCR/ABL oncogenic potential by regulating MYC mRNA translation Blood, March 15, 2006; 107(6): 2507 - 2516. [Abstract] [Full Text] [PDF] M. K. Tee, J.-L. Vigne, and R. N. Taylor All-Trans Retinoic Acid Inhibits Vascular Endothelial Growth Factor Expression in a Cell Model of Neutrophil Activation Endocrinology, March 1, 2006; 147(3): 1264 - 1270. [Abstract] [Full Text] [PDF] P.-Z. Zheng, K.-K. Wang, Q.-Y. Zhang, Q.-H. Huang, Y.-Z. Du, Q.-H. Zhang, D.-K. Xiao, S.-H. Shen, S. Imbeaud, E. Eveno, et al. Systems analysis of transcriptome and proteome in retinoic acid/arsenic trioxide-induced cell differentiation/apoptosis of promyelocytic leukemia PNAS, May 24, 2005; 102(21): 7653 - 7658. [Abstract] [Full Text] [PDF]

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