PDCD2, a protein whose expression is repressed by BCL6, induces apoptosis in human cells by activation of the caspase cascade.
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.
Baron
Beverly W
BW
Department of Pathology, The University of Chicago, IL 60637, USA. Beverly.Baron@uchospitals.edu
Hyjek
Elizabeth
E
Gladstone
Betty
B
Thirman
Michael J
MJ
Baron
Joseph M
JM
D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism*; D053148:Caspase 3 / Q000378:metabolism*; D061945:Caspase Inhibitors; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry; D020014:K562 Cells; D007668:Kidney / Q000166:cytology; D008223:Lymphoma / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D051560:Proto-Oncogene Proteins c-bcl-6 / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D016335:Zinc Fingers
D051017:Apoptosis Regulatory Proteins; D061945:Caspase Inhibitors; C094601:PDCD2 protein, human; D051560:Proto-Oncogene Proteins c-bcl-6; D034741:RNA, Small Interfering; D011993:Recombinant Fusion Proteins; C505407:CASP3 protein, human; D053148:Caspase 3