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Lighting Up the Pathways to Caspase Activation Using Bimolecular Fluorescence Complementation
Published on: March 5, 2018
PDCD2, a protein whose expression is repressed by BCL6, induces apoptosis in human cells by activation of the caspase
Beverly W Baron1, Elizabeth Hyjek, Betty Gladstone
1Department of Pathology, The University of Chicago, IL 60637, USA. Beverly.Baron@uchospitals.edu
Abstract:
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.
Insights
Programmed cell death-2 (PDCD2) promotes apoptosis in human lymphoma cells, partly via caspase activation. BCL6 repression of PDCD2 may contribute to lymphoma development, suggesting PDCD2 as a potential therapeutic target.
Area of Science:
- Molecular Biology
- Cancer Biology
- Cell Death Research
Background:
- The programmed cell death-2 gene (PDCD2) is a known target of BCL6 repression.
- PDCD2's role in the pathogenesis of human lymphomas was previously suggested.
- Understanding PDCD2's function is crucial for lymphoma research.
Purpose of the Study:
- To investigate the role of PDCD2 in inducing apoptosis in human cell lines.
- To explore the mechanism by which PDCD2 induces apoptosis, including caspase cascade involvement.
- To examine the relationship between BCL6, PDCD2 expression, and apoptosis in lymphoma cells.
Main Methods:
- Transfection of PDCD2-expressing constructs into human cell lines.
- Assessment of apoptosis induction and caspase activation.
- Immunohistochemical analysis of PDCD2 expression in human lymphoid and lymphoma tissues.
- Manipulation of BCL6 activity using a VP16-BCL6 fusion protein.
- Knockdown of PDCD2 expression using small interfering RNA (siRNA).
Main Results:
- PDCD2 expression induces apoptosis in human cell lines, partly through caspase cascade activation.
- Caspase inhibitors were found to block PDCD2-induced apoptosis.
- Immunohistochemistry confirmed these findings in human benign lymphoid and lymphoma tissues.
- Inhibition of BCL6 binding increased PDCD2 expression and apoptosis.
- PDCD2 knockdown inhibited apoptosis in a Burkitt lymphoma cell line.
Conclusions:
- PDCD2 functions to promote apoptosis in various human and mammalian cell lines and tissues, including lymphoma.
- Repression of PDCD2 by BCL6 may lead to reduced apoptosis, contributing to BCL6-associated lymphomatous transformation.
- Targeting PDCD2 expression warrants further investigation for lymphoma treatment strategies.
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