PDCD4 (Programmed Cell Death 4)

2007-08-01   Nancy H Colburn  

Laboratory of Cancer Prevention, National Cancer Institute, Bldg. 576, Rm. 101, Frederick, MD 21702-1201, USA

Identity

HGNC
PDCD4
LOCATION
10q25.2
LOCUSID
27250
ALIAS
H731
FUSION GENES
Show Gene Fusions

DNA/RNA

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.

Proteins

Atlas Image

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.

Mutations

Note

No evidence for mutational inactivation in cancer.

Implicated in

Entity name
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.

Article Bibliography

Pubmed IDLast YearTitleAuthors
120825392002Targeted disruption of c-myb in the chicken pre B-cell line DT40.Appl H et al
97598691998Differential 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 et al
128942332003The transformation suppressor protein Pdcd4 shuttles between nucleus and cytoplasm and binds RNA.Böhm M et al
128986012003Loss of PDCD4 expression in human lung cancer correlates with tumour progression and prognosis.Chen Y et al
105701941999Differentially expressed protein Pdcd4 inhibits tumor promoter-induced neoplastic transformation.Cmarik JL et al
170531472006S6K1- and betaTRCP-mediated degradation of PDCD4 promotes protein translation and cell growth.Dorrello NV et al
171144842006Translational regulation of autoimmune inflammation and lymphoma genesis by programmed cell death 4.Hilliard A et al
160246032005Epidermal expression of the translation inhibitor programmed cell death 4 suppresses tumorigenesis.Jansen AP et al
166485762006Aerosol 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 et al
170604472007Structural basis for inhibition of translation by the tumor suppressor Pdcd4.LaRonde-LeBlanc N et al
172974702007Tumor suppressor Pdcd4 inhibits invasion/intravasation and regulates urokinase receptor (u-PAR) gene expression via Sp-transcription factors.Leupold JH et al
172593492007Programmed cell death-4 tumor suppressor protein contributes to retinoic acid-induced terminal granulocytic differentiation of human myeloid leukemia cells.Ozpolat B et al
163571332005Akt phosphorylates and regulates Pdcd4 tumor suppressor protein.Palamarchuk A et al
113139502001The chicken Pdcd4 gene is regulated by v-Myb.Schlichter U et al
170531352006Signal transduction. Protein synthesis and oncogenesis meet again.Sonenberg N et al
173109952007Structure of the C-terminal MA-3 domain of the tumour suppressor protein Pdcd4 and characterization of its interaction with eIF4A.Waters LC et al
150827832004A 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 et al
124829582003The transformation suppressor Pdcd4 is a novel eukaryotic translation initiation factor 4A binding protein that inhibits translation.Yang HS et al
128022782003Pdcd4 suppresses tumor phenotype in JB6 cells by inhibiting AP-1 transactivation.Yang HS et al
164496432006Tumorigenesis suppressor Pdcd4 down-regulates mitogen-activated protein kinase kinase kinase kinase 1 expression to suppress colon carcinoma cell invasion.Yang HS et al
125242092003Promising molecular targets for cancer prevention: AP-1, NF-kappa B and Pdcd4.Young MR et al
166829502006Involvement of programmed cell death 4 in transforming growth factor-beta1-induced apoptosis in human hepatocellular carcinoma.Zhang H et al
114941402001Detection of differentially expressed genes in human colon carcinoma cells treated with a selective COX-2 inhibitor.Zhang Z et al

Other Information

Locus ID:

NCBI: 27250
MIM: 608610
HGNC: 8763
Ensembl: ENSG00000150593

Variants:

dbSNP: 27250
ClinVar: 27250
TCGA: ENSG00000150593
COSMIC: PDCD4

RNA/Proteins

Gene IDTranscript IDUniprot
ENSG00000150593ENST00000280154Q53EL6
ENSG00000150593ENST00000393104Q53EL6
ENSG00000150593ENST00000444997Q5VZS7

Expression (GTEx)

0
50
100
150
200
250
300
Adipose - Subcutaneous
Adipose - Visceral
Adrenal Gland
Artery - Aorta
Artery - Tibial
Bladder
Brain - Amygdala
Brain - Anterior cingulate cortex
Brain - Caudate
Brain - Cerebellar Hemisphere
Brain - Cerebellum
Brain - Cortex
Brain - Frontal Cortex
Brain - Hippocampus
Brain - Hypothalamus
Brain - Nucleus accumbens
Brain - Putamen
Brain - Spinal cord
Brain - Substantia nigra
Breast - Mammary Tissue
Cells - Cultured fibroblasts
Cells - EBV - transformed lymphocytes
Cervix - Ectocervix
Cervix - Endocervix
Colon - Sigmoid
Colon - Transverse
Esophagus - Gastroesophageal Junction
Esophagus - Mucosa
Esophagus - Muscularis
Fallopian Tube
Heart - Atrial Appendage
Heart - Left Ventricle
Kidney - Cortex
Kidney - Medulla
Liver
Lung
Minor Salivary Gland
Muscle - Skeletal
Nerve - Tibial
Ovary
Pancreas
Pituitary
Prostate
Skin - Not Sun Exposed
Skin - Sun Exposed
Small Intestine - Terminal Ileum
Spleen
Stomach
Testis
Thyroid
Uterus
Vagina
Whole Blood

Pathways

PathwaySourceExternal ID
Proteoglycans in cancerKEGGhsa05205
Proteoglycans in cancerKEGGko05205
MicroRNAs in cancerKEGGhsa05206
MicroRNAs in cancerKEGGko05206

Protein levels (Protein atlas)

Not detected
Low
Medium
High
cerebral cortex
cerebellum
hippocampus
caudate
thyroid gland
parathyroid gland
adrenal gland
nasopharynx
bronchus
lung
oral mucosa
salivary gland
esophagus
stomach 1
stomach 2
duodenum
small intestine
colon
rectum
liver
gallbladder
pancreas
kidney
urinary bladder
testis
epididymis
seminal vesicle
prostate
vagina
ovary
fallopian tube
endometrium 1
endometrium 2
cervix, uterine
placenta
breast
heart muscle
smooth muscle
skeletal muscle
soft tissue 1
soft tissue 2
adipose tissue
skin 1
skin 2
appendix
spleen
lymph node
tonsil
bone marrow

References

Pubmed IDYearTitleCitations
382539012024MicroRNA-181b-5p Facilitates Thyroid Cancer Growth via Targeting Programmed Cell Death 4.0
382939732024[PDCD4 knockdown ameliorates lipopolysaccharide-induced endothelial cell damage by improving mitochondrial dynamics].0
383249802024PDCD4 deficiency improved 4-vinylcyclohexene dioxide-induced mouse premature ovarian insufficiency.0
386320922024Progress on the relationship between tumor suppressor PDCD4 and diseases based on the analysis of structural characteristics.0
386409812024STAT1 mediated downregulation of the tumor suppressor gene PDCD4, is driven by the atypical cadherin FAT1, in glioblastoma.0
382539012024MicroRNA-181b-5p Facilitates Thyroid Cancer Growth via Targeting Programmed Cell Death 4.0
382939732024[PDCD4 knockdown ameliorates lipopolysaccharide-induced endothelial cell damage by improving mitochondrial dynamics].0
383249802024PDCD4 deficiency improved 4-vinylcyclohexene dioxide-induced mouse premature ovarian insufficiency.0
386320922024Progress on the relationship between tumor suppressor PDCD4 and diseases based on the analysis of structural characteristics.0
386409812024STAT1 mediated downregulation of the tumor suppressor gene PDCD4, is driven by the atypical cadherin FAT1, in glioblastoma.0
363668422023Gastric Cancer Growth Modulated by circSNTB2/miR-6938-5p/G0S2 and PDCD4.0
365225232023Induction of premature senescence and a less-fibrogenic phenotype by programmed cell death 4 knockdown in the human hepatic stellate cell line Lieming Xu-2.0
368260852023Tumor Suppressor p53 Down-Regulates Programmed Cell Death Protein 4 (PDCD4) Expression.2
370882782023Upregulated MicroRNA-21 Drives the Proliferation of Lymphatic Malformation Endothelial Cells by Inhibiting PDCD4.0
373082772023MiR-93-5p inhibits retinal neurons apoptosis by regulating PDCD4 in acute ocular hypertension model.1

Citation

Nancy H Colburn

PDCD4 (Programmed Cell Death 4)

Atlas Genet Cytogenet Oncol Haematol. 2007-08-01

Online version: http://atlasgeneticsoncology.org/gene/41675/gene-fusions-explorer/favicon/cancer-prone-explorer/