PDCD4 explained

Programmed cell death protein 4 is a protein that in humans is encoded by the PDCD4 gene.^[1] It is one of the targets of an oncomiR, MIRN21.^[2]

Function

This gene encodes a protein localized to the nucleus in proliferating cells. Expression of this gene is modulated by cytokines in natural killer and T cells. The gene product is thought to play a role in apoptosis but the specific role has not yet been determined. Two transcripts encoding different isoforms have been identified.

Interactions

PDCD4 has been shown to interact with RPS13,^[3] ribosomal protein L5, ^[3] p62, LC3 and Ubiquitin [9]

References

9. Manirujjaman M, Ozaki I, Murata Y, Guo J, Xia J, Nishioka K, Perveen R,Takahashi H, Anzai K, Matsuhashi S (2020). "Degradation of the Tumor Suppressor PDCD4 Is Impaired by the Suppression of p62/SQSTM1 and Autophagy". Cells. 9(1): 218. doi.org/10.3390/cells9010218.

Further reading

• Göke R, Gregel C, Göke A, Arnold R, Schmidt H, Lankat-Buttgereit B . Programmed Cell Death Protein 4 (PDCD4) Acts As a Tumor Suppressor in Neuroendocrine Tumor Cells . Annals of the New York Academy of Sciences . 1014 . 220–1 . 2004 . 1 . 15153438 . 10.1196/annals.1294.024 . 2004NYASA1014..220G . 9284462 .
• Maruyama K, Sugano S . Oligo-capping: A simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides . Gene . 138 . 1–2 . 171–4 . 1994 . 8125298 . 10.1016/0378-1119(94)90802-8 .
• Shibahara K, Asano M, Ishida Y, Aoki T, Koike T, Honjo T . Isolation of a novel mouse gene MA-3 that is induced upon programmed cell death . Gene . 166 . 2 . 297–301 . 1995 . 8543179 . 10.1016/0378-1119(95)00607-9 .
• Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S . Construction and characterization of a full length-enriched and a 5′-end-enriched cDNA library . Gene . 200 . 1–2 . 149–56 . 1997 . 9373149 . 10.1016/S0378-1119(97)00411-3 .
• Yoshinaga H, Matsuhashi S, Fujiyama C, Masaki Z . 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 . Pathology International . 49 . 12 . 1067–77 . 1999 . 10632927 . 10.1046/j.1440-1827.1999.00995.x . 968499 .
• 113–4 . 10.1159/000015408 . 10640828 . Assignment¹ of the programmed cell death 4 gene (PDCD4) to human chromosome band 10q24 by in situ hybridization . 1999 . Soejima . H. . Miyoshi . O. . Yoshinaga . H. . Masaki . Z. . Ozaki . I. . Kajiwara . S. . Niikawa . N. . Matsuhashi . S. . Mukai . T. . Cytogenetic and Genome Research . 87. 1–2 . 34560093 .
• Kang MJ, Ahn HS, Lee JY, Matsuhashi S, Park WY . Up-regulation of PDCD4 in senescent human diploid fibroblasts . Biochemical and Biophysical Research Communications . 293 . 1 . 617–21 . 2002 . 12054647 . 10.1016/S0006-291X(02)00264-4 .
• Chen Y, Knösel T, Kristiansen G, Pietas A, Garber ME, Matsuhashi S, Ozaki I, Petersen I . Loss of PDCD4 expression in human lung cancer correlates with tumour progression and prognosis . The Journal of Pathology . 200 . 5 . 640–6 . 2003 . 12898601 . 10.1002/path.1378 . 25899458 .
• Yang HS, Cho MH, Zakowicz H, Hegamyer G, Sonenberg N, Colburn NH . 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 . Molecular and Cellular Biology . 24 . 9 . 3894–906 . 2004 . 15082783 . 387765 . 10.1128/MCB.24.9.3894-3906.2004 .
• Brill LM, Salomon AR, Ficarro SB, Mukherji M, Stettler-Gill M, Peters EC . Robust Phosphoproteomic Profiling of Tyrosine Phosphorylation Sites from Human T Cells Using Immobilized Metal Affinity Chromatography and Tandem Mass Spectrometry . Analytical Chemistry . 76 . 10 . 2763–72 . 2004 . 15144186 . 10.1021/ac035352d .
• Göke R, Barth P, Schmidt A, Samans B, Lankat-Buttgereit B . Programmed cell death protein 4 suppresses CDK1/cdc2 via induction of p21Waf1/Cip1 . AJP: Cell Physiology . 287 . 6 . C1541–6 . 2004 . 15317660 . 10.1152/ajpcell.00025.2004 . 83565566 .
• Rush J, Moritz A, Lee KA, Guo A, Goss VL, Spek EJ, Zhang H, Zha XM, Polakiewicz RD, Comb MJ . Immunoaffinity profiling of tyrosine phosphorylation in cancer cells . Nature Biotechnology . 23 . 1 . 94–101 . 2004 . 15592455 . 10.1038/nbt1046 . 7200157 .
• Rual JF, Venkatesan K, Hao T, Hirozane-Kishikawa T, Dricot A, Li N, Berriz GF, Gibbons FD, Dreze M, Ayivi-Guedehoussou N, Klitgord N, Simon C, Boxem M, Milstein S, Rosenberg J, Goldberg DS, Zhang LV, Wong SL, Franklin G, Li S, Albala JS, Lim J, Fraughton C, Llamosas E, Cevik S, Bex C, Lamesch P, Sikorski RS, Vandenhaute J, Zoghbi HY, Smolyar A, Bosak S, Sequerra R, Doucette-Stamm L, Cusick ME, Hill DE, Roth FP, Vidal M . Towards a proteome-scale map of the human protein–protein interaction network . Nature . 437 . 7062 . 1173–8 . 2005 . 16189514 . 10.1038/nature04209 . 2005Natur.437.1173R . 4427026 . 8 .
• Palamarchuk A, Efanov A, Maximov V, Aqeilan RI, Croce CM, Pekarsky Y . Akt Phosphorylates and Regulates Pdcd4 Tumor Suppressor Protein . Cancer Research . 65 . 24 . 11282–6 . 2005 . 16357133 . 10.1158/0008-5472.CAN-05-3469 . free .
• Yang HS, Matthews CP, Clair T, Wang Q, Baker AR, Li CC, Tan TH, Colburn NH . Tumorigenesis Suppressor Pdcd4 Down-Regulates Mitogen-Activated Protein Kinase Kinase Kinase Kinase 1 Expression to Suppress Colon Carcinoma Cell Invasion . Molecular and Cellular Biology . 26 . 4 . 1297–306 . 2006 . 16449643 . 1367180 . 10.1128/MCB.26.4.1297-1306.2006 .

Notes and References

1. Azzoni L, Zatsepina O, Abebe B, Bennett IM, Kanakaraj P, Perussia B . Differential transcriptional regulation of CD161 and a novel gene, 197/15a, by IL-2, IL-15, and IL-12 in NK and T cells . Journal of Immunology . 161 . 7 . 3493–500 . 1998 . 10.4049/jimmunol.161.7.3493 . 9759869 . 21776266 .
2. Frankel LB, Christoffersen NR, Jacobsen A, Lindow M, Krogh A, Lund AH . Programmed cell death 4 (PDCD4) is an important functional target of the microRNA miR-21 in breast cancer cells . The Journal of Biological Chemistry . 283 . 2 . 1026–33 . 2008 . 17991735 . 10.1074/jbc.M707224200 . free .
3. Kang MJ, Ahn HS, Lee JY, Matsuhashi S, Park WY . Up-regulation of PDCD4 in senescent human diploid fibroblasts . Biochemical and Biophysical Research Communications . 293 . 1 . 617–21 . 2002 . 12054647 . 10.1016/S0006-291X(02)00264-4 .