Alternative titles; symbols
HGNC Approved Gene Symbol: PDCD2
Cytogenetic location: 6q27 Genomic coordinates (GRCh38) : 6:170,575,295-170,584,637 (from NCBI)
Programmed cell death is an essential mechanism of organismal development. The phenomenon can be demonstrated in immature thymocytes, which undergo programmed cell death when treated with glucocorticoid (Wyllie, 1980) or irradiation (Sellins and Cohen, 1987). Programmed cell death in immature thymocytes can be prevented by inhibitors of transcription or translation (Cohen and Duke, 1984). These findings imply that certain kinds of proteins are required to carry out death programs in cells. Some genes are known to be expressed specifically during programmed cell death. In rats, the Rp8 gene, which is transiently expressed in immature thymocytes, is thought to be involved in programmed cell death (Owens and Cohen, 1992). Kawakami et al. (1995) isolated a human cDNA clone from a fetal lung cDNA library that is highly homologous to rat Rp8. The cDNA for the gene, designated PDCD2, contained an open reading frame of 1,032 bp encoding 344 amino acids; it showed 81% identity in DNA sequence and 83% identity in amino acid sequence to rat Rp8. The PDCD2 gene was expressed in all human tissues examined.
BCL6 (109565) encodes a Kruppel-type zinc finger transcriptional repressor. Rearrangements of this gene are frequent in various kinds of lymphomas, particularly of the large-cell B-cell type. The BCL6 nuclear phosphoprotein is expressed in a variety of tissues and is upregulated particularly in lymph node germinal centers. The zinc fingers of BCL6 bind DNA in a sequence-specific manner. To identify targets of the BCL6 repressive effects, Baron et al. (2002) used a fusion protein of BCL6 and an activating domain of herpes simplex virus containing the zinc fingers but devoid of the repressor domains to compete with the binding of endogenous BCL6 in a transiently transfected B-cell line and then performed subtractive hybridization to selectively amplify sequences that are differentially expressed. They found that the PDCD2 gene is a target of BCL6 repression. As noted, PDCD2 is the human homolog of Rp8, a rat gene associated with programmed cell death in thymocytes. Immunohistochemistry demonstrated the anticipated inverse relationship between BCL6 and PDCD2 expression in human tonsils. The results raised the possibility that BCL6 may regulate apoptosis by means of its repressive effects on PDCD2. BCL6 deregulation may lead to persistent downregulation of PDCD2, reduced apoptosis, and, as a consequence, accumulation of BCL6-containing lymphoma cells.
Using EMSA, Baron et al. (2007) showed that BCL6 bound directly to the PDCD2 promoter and repressed its transcription. Small interfering RNA-mediated knockdown of BCL6 in a B-cell lymphoma line resulted in increased PDCD2 protein expression. Mice overexpressing human BCL6 had minimal Pdcd2. Immunohistochemical analysis demonstrated an inverse relationship of PDCD2 and BCL6 expression in human B and T lymphomas. Baron et al. (2007) concluded that PDCD2 is a target of BCL6 and that PDCD2 repression by BCL6 is important in the pathogenesis of certain human lymphomas.
By fluorescence in situ hybridization, Kawakami et al. (1995) mapped PDCD2 gene to 6q27. Trachtulec and Forejt (2001) mapped the Pdcd2 gene to mouse chromosome 17. The orthologs of this and other mouse chromosome 17 genes are located on chromosome III of C. elegans, thus defining a syntenic group conserved between vertebrates and invertebrates. In human, mouse, and snake, the PDCD2 and TBP (600075) genes are adjacent tail to tail. The TBP and PDCD2 genes are linked also in Drosophila and they are syntenic in human, mouse, C. elegans, and S. pombe.
Baron, B. W., Anastasi, J., Thirman, M. J., Furukawa, Y., Fears, S., Kim, D. C., Simone, F., Birkenbach, M., Montag, A., Sadhu, A., Zeleznik-Le, N., McKeithan, T. W. The human programmed cell death-2 (PDCD2) gene is a target of BCL6 repression: implications for a role of BCL6 in the down-regulation of apoptosis. Proc. Nat. Acad. Sci. 99: 2860-2865, 2002. [PubMed: 11854457] [Full Text: https://doi.org/10.1073/pnas.042702599]
Baron, B. W., Zeleznik-Le, N., Baron, M. J., Theisler, C., Huo, D., Krasowski, M. D., Thirman, M. J., Baron, R. M., Baron, J. M. Repression of the PDCD2 gene by BCL6 and the implications for the pathogenesis of human B and T cell lymphomas. Proc. Nat. Acad. Sci. 104: 7449-7454, 2007. [PubMed: 17468402] [Full Text: https://doi.org/10.1073/pnas.0701770104]
Cohen, J. J., Duke, R. C. Glucocorticoid activation of a calcium-dependent endonuclease in thymocyte nuclei leads to cell death. J. Immun. 132: 38-42, 1984. [PubMed: 6317746]
Kawakami, T., Furukawa, Y., Sudo, K., Saito, H., Takami, S., Takahashi, E., Nakamura, Y. Isolation and mapping of a human gene (PDCD2) that is highly homologous to Rp8, a rat gene associated with programmed cell death. Cytogenet. Cell Genet. 71: 41-43, 1995. [PubMed: 7606924] [Full Text: https://doi.org/10.1159/000134058]
Owens, G. P., Cohen, J. J. Identification of genes involved in programmed cell death. Cancer Metastasis Rev. 11: 149-156, 1992. [PubMed: 1394794] [Full Text: https://doi.org/10.1007/BF00048061]
Sellins, K. S., Cohen, J. J. Gene induction by gamma-irradiation leads to DNA fragmentation in lymphocytes. J. Immun. 139: 3199-3206, 1987. [PubMed: 3680944]
Trachtulec, Z., Forejt, J. Synteny of orthologous genes conserved in mammals, snake, fly, nematode, and fission yeast. Mammalian Genome 12: 227-231, 2001. [PubMed: 11252172] [Full Text: https://doi.org/10.1007/s003350010259]
Wyllie, A. H. Glucocorticoid-induced thymocyte apoptosis is associated with endogenous endonuclease activation. Nature 284: 555-556, 1980. [PubMed: 6245367] [Full Text: https://doi.org/10.1038/284555a0]