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Blood, 1 November 2007, Vol. 110, No. 9, pp. 3301-3309. Prepublished online as a Blood First Edition Paper on August 1, 2007August 10, 2007; DOI 10.1182/blood-2007-01-071035. This Article Full Text (PDF) Supplemental Table and Figures All Versions of this Article: blood-2007-01-071035v1 blood-2007-01-071035v2 110/9/3301    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 Geletu, M. Articles by Behre, G. Search for Related Content PubMed PubMed Citation Articles by Geletu, M. Articles by Behre, G. Related Collections Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted January 30, 2007 Accepted July 10, 2007 Target proteins of C/EBP-p30 in AML: C/EBP-p30 enhances Sumoylation of C/EBP-p42 via up regulation of Ubc9 Mulu Geletu, Mumtaz Yaseen Balkhi, Abdul Ali Peer Zada, Maximilian Christopeit, John Anto Pulikkan, Arun Kumar Trivedi, Daniel G. Tenen, and Gerhard Behre* Dept of Internal Medicine IV-Hematology/Oncology BMT Section, State Center for Cell & Gene Therapy, Univ. Hospital of Martin-Luther-Univ Halle-Wittenberg, Halle, Germany Division of Hematology/Oncology, Harvard Institutes of Medicine, Boston, MA, United States * Corresponding author; email: gerhard.behre{at}medizin.uni-halle.de. CCAAT/enhancer-binding protein alpha (C/EBP) is a critical regulator for early myeloid differentiation. Mutations in C/EBP occur in 10% of AML patients, leading to the expression of a 30kDa dominant negative isoform (C/EBPp30). In the present study, using a global proteomics approach to identify the target proteins of C/EBPp30, we show that Ubc9, an E2 conjugating enzyme, essential for sumoylation is increased in its expression when C/EBPp30 is induced. We confirmed the increased expression of Ubc9 in AML patients with C/EBPp30 mutations compared with other subtypes. We further confirmed that the increase of Ubc9 expression was mediated through increased transcription. Furthermore, we show that Ubc9 mediated enhanced sumoylation of C/EBPp42 decreases the transactivation capacity on a minimal C/EBP promoter. Importantly, overexpression of C/EBPp30 in G-CSF stimulated human CD34+ cells leads to a differentiation block, which was overcome by the siRNA mediated silencing of Ubc9. In summary, our data indicate Ubc9 as an important C/EBPp30 target through which C/EBPp30 enhances the sumoylation of C/EBPp42 to inhibit granulocytic differentiation. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: C/EBPp30 SUMO wrestles C/EBPp42 Richard Dahl Blood 2007 110: 3089. [Full Text] [PDF] This article has been cited by other articles: T. Pabst and B. U. Mueller Complexity of CEBPA Dysregulation in Human Acute Myeloid Leukemia Clin. Cancer Res., September 1, 2009; 15(17): 5303 - 5307. [Abstract] [Full Text] [PDF] S. Koschmieder, B. Halmos, E. Levantini, and D. G. Tenen Dysregulation of the C/EBP{alpha} Differentiation Pathway in Human Cancer J. Clin. Oncol., February 1, 2009; 27(4): 619 - 628. [Abstract] [Full Text] [PDF] M. Han, W. Yan, Y. Huang, H. Yao, Z. Wang, D. Xi, W. Li, Y. Zhou, J. Hou, X. Luo, et al. The Nucleocapsid Protein of SARS-CoV Induces Transcription of hfgl2 Prothrombinase Gene Dependent on C/EBP Alpha J. Biochem., July 1, 2008; 144(1): 51 - 62. [Abstract] [Full Text] [PDF]

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