Studies from Martin-Luther University, Center for Cell and Gene Therapy update current data on life sciences
2007 NOV 19 -- A report, 'Target proteins of C/EBPalphap30 in AML: C/EBPalphap30 enhances sumoylation of C/EBPalphap42 via up-regulation of Ubc9,' is newly published data in Blood. "CCAAT/enhancer-binding protein alpha (C/EBPalpha) is a critical regulator for early myeloid differentiation. Mutations in C/EBPalpha occur in 10% of patients with acute myeloid leukemia (AML), leading to the expression of a 30-kDa dominant-negative isoform (C/EBPalphap30)," scientists in Halle, Germany report. "In the present study, using a global proteomics approach to identify the target proteins of C/EBPalphap30, we show that Ubc9, an E2-conjugating enzyme essential for sumoylation, is increased in its expression when C/EBPalphap30 is induced. We confirmed the increased expression of Ubc9 in patients with AML with C/EBPalphap30 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/EBPalphap42 decreases the transactivation capacity on a minimal C/EBPalpha promoter. Importantly, overexpression of C/EBPalphap30 in granulocyte colony-stimulating factor (G-CSF)-stimulated human CD34(+) cells leads to a differentiation block, which was overcome by the siRNA-mediated silencing of Ubc9," wrote M. Geletu and colleagues, Martin-Luther University, Center for Cell and Gene Therapy. The researchers concluded: "In summary, our data indicate that Ubc9 is an important C/EBPalphap30 target through which C/EBPalphap30 enhances the sumoylation of C/EBPalphap42 to inhibit granulocytic differentiation." Geletu and colleagues published their study in Blood (Target proteins of C/EBPalphap30 in AML: C/EBPalphap30 enhances sumoylation of C/EBPalphap42 via up-regulation of Ubc9. Blood, 2007;110(9):3301-9). For more information, contact M. Geletu, Bone Marrow Transplantation Section, Dept. of Internal Medicine IV-Hematology, State Center for Cell and Gene Therapy, Oncology, University Hospital of Martin-Luther-University Halle-Wittenberg, Ernst-Grube-Strasse 40, 06120 Halle, Germany. Publisher contact information for the journal Blood is: American Society Hematology, 1900 M Street. NW Suite 200, Washington, DC 20036, USA. Keywords: Germany, Halle, Life Sciences, Treatment, Therapy. This article was prepared by Biotech Business Week editors from staff and other reports. Copyright 2007, Biotech Business Week via NewsRx.com.
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