PDCD2, a protein whose expression is repressed by BCL6, induces apoptosis in human cells by activation of the caspase cascade
| Autor: | Elizabeth Hyjek, Michael J. Thirman, Joseph M. Baron, Betty Gladstone, Beverly W. Baron |
|---|---|
| Rok vydání: | 2010 |
| Předmět: |
Small interfering RNA
Lymphoma Recombinant Fusion Proteins Apoptosis Caspase 3 Kidney immune system diseases hemic and lymphatic diseases Humans RNA Small Interfering Molecular Biology Caspase biology NLRP1 Zinc Fingers Cell Biology Hematology Transfection BCL6 Caspase Inhibitors Immunohistochemistry BCL10 Cell biology Gene Expression Regulation Neoplastic Proto-Oncogene Proteins c-bcl-6 Cancer research biology.protein Molecular Medicine Apoptosis Regulatory Proteins K562 Cells |
| Zdroj: | Blood Cells, Molecules, and Diseases. 45:169-175 |
| ISSN: | 1079-9796 |
| Popis: | We have previously reported that the human programmed cell death-2 gene (PDCD2), a target of BCL6 repression, is likely to be important in the pathogenesis of certain human lymphomas. We now demonstrate that transfection of a construct expressing PDCD2 induces apoptosis in human cell lines, that this occurs, at least in part, through activation of the caspase cascade, and, furthermore, that caspase inhibitors block this effect. Immunohistochemical studies in human benign lymphoid and lymphoma tissues support these findings. In addition, transfection of a VP16-BCL6 zinc fingers fusion protein, which competes with the binding of endogenous BCL6 in a Burkitt lymphoma cell line, increases PDCD2 protein expression and apoptosis, and knockdown of the PDCD2 protein in this cell line by PDCD2-specific small interfering RNA duplexes inhibits apoptosis. These studies indicate that one function of PDCD2 is to promote apoptosis in several human and mammalian cell lines and tissues, including lymphoma. Although the pathways involved in lymphomagenesis are likely to be multiple and complex, it is plausible that repression of PDCD2 expression by BCL6, which, in turn, leads to downregulation of apoptosis, is one mechanism involved in BCL6-associated lymphomatous transformation. The usefulness of increasing PDCD2 expression in the treatment of certain lymphomas merits further investigation. |
| Databáze: | OpenAIRE |
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