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Gene Review

PDCD4  -  programmed cell death 4 (neoplastic...

Homo sapiens

Synonyms: H731, Neoplastic transformation inhibitor protein, Nuclear antigen H731-like, Programmed cell death protein 4, Protein 197/15a
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Disease relevance of PDCD4


High impact information on PDCD4


Chemical compound and disease context of PDCD4


Biological context of PDCD4


Anatomical context of PDCD4


Associations of PDCD4 with chemical compounds

  • Other granulocytic differentiation inducers such as DMSO and arsenic trioxide also induced PDCD4 expression in NB4 cells [2].
  • Phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) signaling pathway was found to regulate PDCD4 expression because inhibition of PI3K by LY294002 and wortmannin or of mTOR by rapamycin induced PDCD4 protein and mRNA expression [2].
  • Similar to pdcd4, carbonic anhydrase inhibitor ethoxyzolamide reduces growth of several endocrine tumor cell lines [17].
  • Thus, up-regulating Pdcd4 expression may be promising for geldanamycin-based combination therapy [11].
  • Knockdown of PDCD4 expression results in reversal of the suppressive effects of nilotinib and imatinib mesylate on leukemic progenitor colony formation, suggesting an important role for this protein in the generation of antileukemic responses [18].

Physical interactions of PDCD4

  • Several eIF4A mutants showing wild-type level binding to Pdcd4 were also inactivated for binding to eIF4G and for enhancing translation [19].

Other interactions of PDCD4

  • Thus, Pdcd4 suppresses tumor progression in human colon carcinoma cells by the novel mechanism of down-regulating MAP4K1 transcription, with consequent inhibition of c-Jun activation and AP-1-dependent transcription [7].
  • Additionally, under-expressed genes encoded apoptosis-related proteins (PDCD4 and CASP4) [20].
  • Induction of PDCD4 tumor suppressor gene expression by RAR agonists, antiestrogen and HER-2/neu antagonist in breast cancer cells. Evidence for a role in apoptosis [10].
  • We identified additional genes which are involved in different signaling pathways which regulate programmed cell death (Dynamin 2, Pdcd4 and LIP.1) [21].

Analytical, diagnostic and therapeutic context of PDCD4


  1. Programmed cell death protein 4 (PDCD4) acts as a tumor suppressor in neuroendocrine tumor cells. Göke, R., Gregel, C., Göke, A., Arnold, R., Schmidt, H., Lankat-Buttgereit, B. Ann. N. Y. Acad. Sci. (2004) [Pubmed]
  2. Programmed cell death-4 tumor suppressor protein contributes to retinoic Acid-induced terminal granulocytic differentiation of human myeloid leukemia cells. Ozpolat, B., Akar, U., Steiner, M., Zorrilla-Calancha, I., Tirado-Gomez, M., Colburn, N., Danilenko, M., Kornblau, S., Lopez Berestein, G. Mol. Cancer Res. (2007) [Pubmed]
  3. Programmed cell death protein 4 suppresses CDK1/cdc2 via induction of p21(Waf1/Cip1). Göke, R., Barth, P., Schmidt, A., Samans, B., Lankat-Buttgereit, B. Am. J. Physiol., Cell Physiol. (2004) [Pubmed]
  4. Frequent loss of PDCD4 expression in human glioma: Possible role in the tumorigenesis of glioma. Gao, F., Zhang, P., Zhou, C., Li, J., Wang, Q., Zhu, F., Ma, C., Sun, W., Zhang, L. Oncol. Rep. (2007) [Pubmed]
  5. Tumor suppressor Pdcd4 inhibits invasion/intravasation and regulates urokinase receptor (u-PAR) gene expression via Sp-transcription factors. Leupold, J.H., Yang, H.S., Colburn, N.H., Asangani, I., Post, S., Allgayer, H. Oncogene (2007) [Pubmed]
  6. Structural basis for inhibition of translation by the tumor suppressor Pdcd4. LaRonde-LeBlanc, N., Santhanam, A.N., Baker, A.R., Wlodawer, A., Colburn, N.H. Mol. Cell. Biol. (2007) [Pubmed]
  7. Tumorigenesis suppressor Pdcd4 down-regulates mitogen-activated protein kinase kinase kinase kinase 1 expression to suppress colon carcinoma cell invasion. Yang, H.S., Matthews, C.P., Clair, T., Wang, Q., Baker, A.R., Li, C.C., Tan, T.H., Colburn, N.H. Mol. Cell. Biol. (2006) [Pubmed]
  8. A novel function of the MA-3 domains in transformation and translation suppressor Pdcd4 is essential for its binding to eukaryotic translation initiation factor 4A. Yang, H.S., Cho, M.H., Zakowicz, H., Hegamyer, G., Sonenberg, N., Colburn, N.H. Mol. Cell. Biol. (2004) [Pubmed]
  9. Akt phosphorylates and regulates Pdcd4 tumor suppressor protein. Palamarchuk, A., Efanov, A., Maximov, V., Aqeilan, R.I., Croce, C.M., Pekarsky, Y. Cancer Res. (2005) [Pubmed]
  10. Induction of PDCD4 tumor suppressor gene expression by RAR agonists, antiestrogen and HER-2/neu antagonist in breast cancer cells. Evidence for a role in apoptosis. Afonja, O., Juste, D., Das, S., Matsuhashi, S., Samuels, H.H. Oncogene (2004) [Pubmed]
  11. Characterization of programmed cell death 4 in multiple human cancers reveals a novel enhancer of drug sensitivity. Jansen, A.P., Camalier, C.E., Stark, C., Colburn, N.H. Mol. Cancer Ther. (2004) [Pubmed]
  12. Up-regulation of PDCD4 in senescent human diploid fibroblasts. Kang, M.J., Ahn, H.S., Lee, J.Y., Matsuhashi, S., Park, W.Y. Biochem. Biophys. Res. Commun. (2002) [Pubmed]
  13. Assignment of the programmed cell death 4 gene (PDCD4) to human chromosome band 10q24 by in situ hybridization. Soejima, H., Miyoshi, O., Yoshinaga, H., Masaki, Z., Ozaki, I., Kajiwara, S., Niikawa, N., Matsuhashi, S., Mukai, T. Cytogenet. Cell Genet. (1999) [Pubmed]
  14. Involvement of programmed cell death 4 in transforming growth factor-beta1-induced apoptosis in human hepatocellular carcinoma. Zhang, H., Ozaki, I., Mizuta, T., Hamajima, H., Yasutake, T., Eguchi, Y., Ideguchi, H., Yamamoto, K., Matsuhashi, S. Oncogene (2006) [Pubmed]
  15. Novel human PDCD4 (H731) gene expressed in proliferative cells is expressed in the small duct epithelial cells of the breast as revealed by an anti-H731 antibody. Yoshinaga, H., Matsuhashi, S., Fujiyama, C., Masaki, Z. Pathol. Int. (1999) [Pubmed]
  16. Translational regulation of autoimmune inflammation and lymphoma genesis by programmed cell death 4. Hilliard, A., Hilliard, B., Zheng, S.J., Sun, H., Miwa, T., Song, W., G??ke, R., Chen, Y.H. J. Immunol. (2006) [Pubmed]
  17. Pdcd4 inhibits growth of tumor cells by suppression of carbonic anhydrase type II. Lankat-Buttgereit, B., Gregel, C., Knolle, A., Hasilik, A., Arnold, R., Göke, R. Mol. Cell. Endocrinol. (2004) [Pubmed]
  18. Suppression of programmed cell death 4 (PDCD4) protein expression by BCR-ABL-regulated engagement of the mTOR/p70 S6 kinase pathway. Carayol, N., Katsoulidis, E., Sassano, A., Altman, J.K., Druker, B.J., Platanias, L.C. J. Biol. Chem. (2008) [Pubmed]
  19. Mutational analysis of the DEAD-box RNA helicase eIF4AII characterizes its interaction with transformation suppressor Pdcd4 and eIF4GI. Zakowicz, H., Yang, H.S., Stark, C., Wlodawer, A., Laronde-Leblanc, N., Colburn, N.H. RNA (2005) [Pubmed]
  20. Potential markers of tongue tumor progression selected by cDNA microarray. Carinci, F., Lo Muzio, L., Piattelli, A., Rubini, C., Chiesa, F., Ionna, F., Palmieri, A., Maiorano, E., Pastore, A., Laino, G., Dolci, M., Pezzetti, F. International journal of immunopathology and pharmacology. (2005) [Pubmed]
  21. Detection of differentially expressed genes in human colon carcinoma cells treated with a selective COX-2 inhibitor. Zhang, Z., DuBois, R.N. Oncogene (2001) [Pubmed]
  22. Loss of PDCD4 expression in human lung cancer correlates with tumour progression and prognosis. Chen, Y., Knösel, T., Kristiansen, G., Pietas, A., Garber, M.E., Matsuhashi, S., Ozaki, I., Petersen, I. J. Pathol. (2003) [Pubmed]
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