Atlas of Genetics and Cytogenetics in Oncology and Haematology

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PDCD4 (Programmed Cell Death 4)

Written2007-08Nancy H Colburn
Laboratory of Cancer Prevention, National Cancer Institute, Bldg. 576, Rm. 101, Frederick, MD 21702-1201, USA

(Note : for Links provided by Atlas : click)


Alias_symbol (synonym)H731
Other aliasTIS
LocusID (NCBI) 27250
Atlas_Id 41675
Location 10q25.2  [Link to chromosome band 10q25]
Location_base_pair Starts at 112631553 and ends at 112659764 bp from pter ( according to hg19-Feb_2009)  [Mapping PDCD4.png]
Fusion genes
(updated 2016)
PDCD4 (10q25.2) / CHD1L (1q21.1)PDCD4 (10q25.2) / CHRM3 (1q43)PDCD4 (10q25.2) / GAPDH (12p13.31)
PDCD4 (10q25.2) / LOC338799 ()PDCD4 (10q25.2) / PDCD4 (10q25.2)PDCD4 (10q25.2) / PMS2P5 ()
PDCD4 (10q25.2) / UBE2N (12q22)STEAP2 (7q21.13) / PDCD4 (10q25.2)


Description Single gene of 11 exons spanning 21 Kbp.
Transcription 2.4 Kb mRNA; PDCD4 mRNA levels modulated by apoptosis inducers, retinoids, and other extracellular signals.
Pseudogene None.


Description 469 amino acids; 52 kDa predicted; found to be 50-64 kDa in mouse and human tissues and cell lines; contains two highly conserved helical MA3 domains each about 130 amino acids long; contains two Akt/S6K phosphorylation sites, one N-terminal and one C-terminal; contains two nuclear export signals.
Expression PDCD4 expressed in all tissues tested. Shows inverse expression with proliferation marker PCNA, higher expression in differentiated areas. Protein expression is regulated by PI3K/Akt/S6K and MEK/ERK signaling that programs PDCD4 for ubiquitylation and proteasome degradation.
Localisation Nuclear and cytoplasmic. Inhibits translation in cytoplasm.
Function PDCD4 inhibits translation initiation mRNA-specifically by interacting with translation initiation factor eIF4A and competing with eIF4Gc for binding to eIF4A. As a consequence of inhibiting translation initiation, inhibits AP-1 dependent transcription via targeting Jun kinase signaling. Found to be a tumor suppressor in PDCD4 transgenic and deficient mice.
Homology Conserved MA3 domain also found in translation initiation factor eIF4G, a scaffold protein; death associated protein DAP5; and NOM 1, a nucleolar protein.


Note No evidence for mutational inactivation in cancer.

Implicated in

Entity Human tumors
Disease PDCD4 expression attenuated with progression in human tumors of the lung, colon, prostate and breast; diagnostic and prognostic for colon cancer staging with decreased expression in adenomas and a further decrease in stage 1 adenocarcinomas. Transgenic PDCD4 expression attenuates skin tumorigenesis and tumor progression in transgenic mice; PDCD4 deficiency increases tumor multiplicity and tumor incidence.


Targeted disruption of c-myb in the chicken pre B-cell line DT40.
Appl H, Klempnauer KH
Oncogene. 2002 ; 21 (19) : 3076-3081.
PMID 12082539
Differential transcriptional regulation of CD161 and a novel gene, 197/15a, by IL-2, IL-15, and IL-12 in NK and T cells.
Azzoni L, Zatsepina O, Abebe B, Bennett IM, Kanakaraj P, Perussia B
Journal of immunology (Baltimore, Md. : 1950). 1998 ; 161 (7) : 3493-3500.
PMID 9759869
The transformation suppressor protein Pdcd4 shuttles between nucleus and cytoplasm and binds RNA.
Böhm M, Sawicka K, Siebrasse JP, Brehmer-Fastnacht A, Peters R, Klempnauer KH
Oncogene. 2003 ; 22 (31) : 4905-4910.
PMID 12894233
Loss of PDCD4 expression in human lung cancer correlates with tumour progression and prognosis.
Chen Y, Knösel T, Kristiansen G, Pietas A, Garber ME, Matsuhashi S, Ozaki I, Petersen I
The Journal of pathology. 2003 ; 200 (5) : 640-646.
PMID 12898601
Differentially expressed protein Pdcd4 inhibits tumor promoter-induced neoplastic transformation.
Cmarik JL, Min H, Hegamyer G, Zhan S, Kulesz-Martin M, Yoshinaga H, Matsuhashi S, Colburn NH
Proceedings of the National Academy of Sciences of the United States of America. 1999 ; 96 (24) : 14037-14042.
PMID 10570194
S6K1- and betaTRCP-mediated degradation of PDCD4 promotes protein translation and cell growth.
Dorrello NV, Peschiaroli A, Guardavaccaro D, Colburn NH, Sherman NE, Pagano M
Science (New York, N.Y.). 2006 ; 314 (5798) : 467-471.
PMID 17053147
Translational regulation of autoimmune inflammation and lymphoma genesis by programmed cell death 4.
Hilliard A, Hilliard B, Zheng SJ, Sun H, Miwa T, Song W, Göke R, Chen YH
Journal of immunology (Baltimore, Md. : 1950). 2006 ; 177 (11) : 8095-8102.
PMID 17114484
Epidermal expression of the translation inhibitor programmed cell death 4 suppresses tumorigenesis.
Jansen AP, Camalier CE, Colburn NH
Cancer research. 2005 ; 65 (14) : 6034-6041.
PMID 16024603
Aerosol delivery of urocanic acid-modified chitosan/programmed cell death 4 complex regulated apoptosis, cell cycle, and angiogenesis in lungs of K-ras null mice.
Jin H, Kim TH, Hwang SK, Chang SH, Kim HW, Anderson HK, Lee HW, Lee KH, Colburn NH, Yang HS, Cho MH, Cho CS
Molecular cancer therapeutics. 2006 ; 5 (4) : 1041-1049.
PMID 16648576
Structural basis for inhibition of translation by the tumor suppressor Pdcd4.
LaRonde-LeBlanc N, Santhanam AN, Baker AR, Wlodawer A, Colburn NH
Molecular and cellular biology. 2007 ; 27 (1) : 147-156.
PMID 17060447
Tumor suppressor Pdcd4 inhibits invasion/intravasation and regulates urokinase receptor (u-PAR) gene expression via Sp-transcription factors.
Leupold JH, Yang HS, Colburn NH, Asangani I, Post S, Allgayer H
Oncogene. 2007 ; 26 (31) : 4550-4562.
PMID 17297470
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, Berestein GL
Molecular cancer research : MCR. 2007 ; 5 (1) : 95-108.
PMID 17259349
Akt phosphorylates and regulates Pdcd4 tumor suppressor protein.
Palamarchuk A, Efanov A, Maximov V, Aqeilan RI, Croce CM, Pekarsky Y
Cancer research. 2005 ; 65 (24) : 11282-11286.
PMID 16357133
The chicken Pdcd4 gene is regulated by v-Myb.
Schlichter U, Burk O, Worpenberg S, Klempnauer KH
Oncogene. 2001 ; 20 (2) : 231-239.
PMID 11313950
Signal transduction. Protein synthesis and oncogenesis meet again.
Sonenberg N, Pause A
Science (New York, N.Y.). 2006 ; 314 (5798) : 428-429.
PMID 17053135
Structure of the C-terminal MA-3 domain of the tumour suppressor protein Pdcd4 and characterization of its interaction with eIF4A.
Waters LC, Veverka V, Böhm M, Schmedt T, Choong PT, Muskett FW, Klempnauer KH, Carr MD
Oncogene. 2007 ; 26 (34) : 4941-4950.
PMID 17310995
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 HS, Cho MH, Zakowicz H, Hegamyer G, Sonenberg N, Colburn NH
Molecular and cellular biology. 2004 ; 24 (9) : 3894-3906.
PMID 15082783
The transformation suppressor Pdcd4 is a novel eukaryotic translation initiation factor 4A binding protein that inhibits translation.
Yang HS, Jansen AP, Komar AA, Zheng X, Merrick WC, Costes S, Lockett SJ, Sonenberg N, Colburn NH
Molecular and cellular biology. 2003 ; 23 (1) : 26-37.
PMID 12482958
Pdcd4 suppresses tumor phenotype in JB6 cells by inhibiting AP-1 transactivation.
Yang HS, Knies JL, Stark C, Colburn NH
Oncogene. 2003 ; 22 (24) : 3712-3720.
PMID 12802278
Tumorigenesis suppressor Pdcd4 down-regulates mitogen-activated protein kinase kinase kinase kinase 1 expression to suppress colon carcinoma cell invasion.
Yang HS, Matthews CP, Clair T, Wang Q, Baker AR, Li CC, Tan TH, Colburn NH
Molecular and cellular biology. 2006 ; 26 (4) : 1297-1306.
PMID 16449643
Promising molecular targets for cancer prevention: AP-1, NF-kappa B and Pdcd4.
Young MR, Yang HS, Colburn NH
Trends in molecular medicine. 2003 ; 9 (1) : 36-41.
PMID 12524209
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 ; 25 (45) : 6101-6112.
PMID 16682950
Detection of differentially expressed genes in human colon carcinoma cells treated with a selective COX-2 inhibitor.
Zhang Z, DuBois RN
Oncogene. 2001 ; 20 (33) : 4450-4456.
PMID 11494140


This paper should be referenced as such :
Colburn, NH
PDCD4 (programmed cell death 4)
Atlas Genet Cytogenet Oncol Haematol. 2008;12(2):125-126.
Free journal version : [ pdf ]   [ DOI ]
On line version :

External links

HGNC (Hugo)PDCD4   8763
Entrez_Gene (NCBI)PDCD4  27250  programmed cell death 4 (neoplastic transformation inhibitor)
GeneCards (Weizmann)PDCD4
Ensembl hg19 (Hinxton)ENSG00000150593 [Gene_View]  chr10:112631553-112659764 [Contig_View]  PDCD4 [Vega]
Ensembl hg38 (Hinxton)ENSG00000150593 [Gene_View]  chr10:112631553-112659764 [Contig_View]  PDCD4 [Vega]
ICGC DataPortalENSG00000150593
TCGA cBioPortalPDCD4
Genatlas (Paris)PDCD4
SOURCE (Princeton)PDCD4
Genetics Home Reference (NIH)PDCD4
Genomic and cartography
GoldenPath hg19 (UCSC)PDCD4  -     chr10:112631553-112659764 +  10q24   [Description]    (hg19-Feb_2009)
GoldenPath hg38 (UCSC)PDCD4  -     10q24   [Description]    (hg38-Dec_2013)
EnsemblPDCD4 - 10q24 [CytoView hg19]  PDCD4 - 10q24 [CytoView hg38]
Mapping of homologs : NCBIPDCD4 [Mapview hg19]  PDCD4 [Mapview hg38]
Gene and transcription
Genbank (Entrez)AK223623 AK296753 AK312540 AK315295 AL049932
RefSeq transcript (Entrez)NM_001199492 NM_014456 NM_145341
RefSeq genomic (Entrez)NC_000010 NC_018921 NT_030059 NW_004929376
Consensus coding sequences : CCDS (NCBI)PDCD4
Cluster EST : UnigeneHs.711490 [ NCBI ]
CGAP (NCI)Hs.711490
Alternative Splicing GalleryENSG00000150593
Gene ExpressionPDCD4 [ NCBI-GEO ]   PDCD4 [ EBI - ARRAY_EXPRESS ]   PDCD4 [ SEEK ]   PDCD4 [ MEM ]
Gene Expression Viewer (FireBrowse)PDCD4 [ Firebrowse - Broad ]
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
GenevisibleExpression in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)27250
GTEX Portal (Tissue expression)PDCD4
Protein : pattern, domain, 3D structure
UniProt/SwissProtQ53EL6   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtQ53EL6  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProQ53EL6
Splice isoforms : SwissVarQ53EL6
Domaine pattern : Prosite (Expaxy)MI (PS51366)   
Domains : Interpro (EBI)ARM-type_fold    Initiation_fac_eIF4g_MI    MIF4-like   
Domain families : Pfam (Sanger)MA3 (PF02847)   
Domain families : Pfam (NCBI)pfam02847   
Domain families : Smart (EMBL)MA3 (SM00544)  
Conserved Domain (NCBI)PDCD4
DMDM Disease mutations27250
Blocks (Seattle)PDCD4
PDB (SRS)2GGF    2KZT    2RG8    2ZU6    3EIJ   
PDB (PDBSum)2GGF    2KZT    2RG8    2ZU6    3EIJ   
PDB (IMB)2GGF    2KZT    2RG8    2ZU6    3EIJ   
PDB (RSDB)2GGF    2KZT    2RG8    2ZU6    3EIJ   
Structural Biology KnowledgeBase2GGF    2KZT    2RG8    2ZU6    3EIJ   
SCOP (Structural Classification of Proteins)2GGF    2KZT    2RG8    2ZU6    3EIJ   
CATH (Classification of proteins structures)2GGF    2KZT    2RG8    2ZU6    3EIJ   
Human Protein AtlasENSG00000150593
Peptide AtlasQ53EL6
IPIIPI00290110   IPI00647084   IPI00240675   
Protein Interaction databases
IntAct (EBI)Q53EL6
Ontologies - Pathways
Ontology : AmiGORNA binding  protein binding  nucleus  nucleus  nucleoplasm  cytoplasm  cytosol  apoptotic process  cell aging  positive regulation of smooth muscle cell apoptotic process  negative regulation of apoptotic process  negative regulation of JUN kinase activity  negative regulation of cell cycle  negative regulation of transcription, DNA-templated  negative regulation of transcription, DNA-templated  negative regulation of myofibroblast differentiation  
Ontology : EGO-EBIRNA binding  protein binding  nucleus  nucleus  nucleoplasm  cytoplasm  cytosol  apoptotic process  cell aging  positive regulation of smooth muscle cell apoptotic process  negative regulation of apoptotic process  negative regulation of JUN kinase activity  negative regulation of cell cycle  negative regulation of transcription, DNA-templated  negative regulation of transcription, DNA-templated  negative regulation of myofibroblast differentiation  
Pathways : KEGGProteoglycans in cancer    MicroRNAs in cancer   
NDEx NetworkPDCD4
Atlas of Cancer Signalling NetworkPDCD4
Wikipedia pathwaysPDCD4
Orthology - Evolution
GeneTree (enSembl)ENSG00000150593
Phylogenetic Trees/Animal Genes : TreeFamPDCD4
Homologs : HomoloGenePDCD4
Homology/Alignments : Family Browser (UCSC)PDCD4
Gene fusions - Rearrangements
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerPDCD4 [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)PDCD4
Exome Variant ServerPDCD4
ExAC (Exome Aggregation Consortium)PDCD4 (select the gene name)
Genetic variants : HAPMAP27250
Genomic Variants (DGV)PDCD4 [DGVbeta]
DECIPHER (Syndromes)10:112631553-112659764  ENSG00000150593
CONAN: Copy Number AnalysisPDCD4 
ICGC Data PortalPDCD4 
TCGA Data PortalPDCD4 
Broad Tumor PortalPDCD4
OASIS PortalPDCD4 [ Somatic mutations - Copy number]
Somatic Mutations in Cancer : COSMICPDCD4  [overview]  [genome browser]  [tissue]  [distribution]  
Mutations and Diseases : HGMDPDCD4
LOVD (Leiden Open Variation Database)Whole genome datasets
LOVD (Leiden Open Variation Database)LOVD - Leiden Open Variation Database
LOVD (Leiden Open Variation Database)LOVD 3.0 shared installation
BioMutasearch PDCD4
DgiDB (Drug Gene Interaction Database)PDCD4
DoCM (Curated mutations)PDCD4 (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)PDCD4 (select a term)
NCG5 (London)PDCD4
Cancer3DPDCD4(select the gene name)
Impact of mutations[PolyPhen2] [SIFT Human Coding SNP] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
Genetic Testing Registry PDCD4
NextProtQ53EL6 [Medical]
Huge Navigator PDCD4 [HugePedia]
snp3D : Map Gene to Disease27250
BioCentury BCIQPDCD4
Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD27250
Chemical/Pharm GKB GenePA33113
Clinical trialPDCD4
canSAR (ICR)PDCD4 (select the gene name)
PubMed194 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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indexed on : Tue Mar 14 13:46:39 CET 2017

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