tailieunhanh - Báo cáo khoa học: E2A participates in a fine control of pre-mature B-cell apoptosis mediated by B-cell receptor signaling via transcriptional regulation of survivin, IAP2 and caspase-8 genes

Dinucleoside polyphosphates (NpnN¢s; where N and N¢ are nucleosides andn= 3–6 phosphate residues) are naturally occurring compounds that may act as signaling molecules. One of the most successful approaches to understand their biological functions has been through the use of NpnN¢ analogs. | E2A participates in a fine control of pre-mature B-cell apoptosis mediated by B-cell receptor signaling via transcriptional regulation of survivin IAP2 and caspase-8 genes Kenji Toyonaga1 2 Hidehiko Kikuchi1 3 Koki Yamashita1 Masami Nakayama1 Kazuo Chijiiwa2 and Tatsuo Nakayama1 3 1 Section of Biochemistry and Molecular Biology Department of MedicalSciences Miyazaki MedicalCollege University of Miyazaki Japan 2 Section of SurgicalOncology and Regulation of Organ Function Department of MedicalScience Miyazaki MedicalCollege University of Miyazaki Japan 3 Department of Life Science Frontier Science Research Center University of Miyazaki Japan Keywords apoptosis B cell caspase E2A survivin Correspondence T. Nakayama Department of Life Science Frontier Science Research Center University of Miyazaki 5200 Kihara Kiyotake Miyazaki 889-1692 Japan Fax 81 985 85 6503 Tel 81 985 85 3127 E-mail tnakayam@ These authors contributed equally to this work Received 8 May 2008 revised 16 December 2008 accepted 24 December 2008 doi Antigen binding to the B-cell receptor BCR of pre-mature B lymphocytes induces their apoptotic cell death but binding to the BCR of mature B lymphocytes triggers activation and proliferation. Binding to pre-mature B lymphocytes is thought not only to function as a mechanism to exclude B-cell clones that possess the ability to react with self-antigen but also to act as a defense mechanism in auto-immune diseases. Cross-linking of BCR of pre-mature B-cell lines including the chicken DT40 cell line with anti-immunoglobulin IgG induces apoptotic cell death. Treatment with phorbol 12-myristate 13-acetate ionomycin which mimics BCR stimulation is used to study intracellular signal transduction of B lymphocytes. Here by analyzing the E2A-deficient DT40 cell line E2A we show that E2A deficiency prevents certain levels of apoptotic cell death mediated by BCR signaling. In addition E2A deficiency-linked BCR .