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
LOCATION
10q25.2
LOCUSID
ALIAS
H731
FUSION GENES

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.

Bibliography

Pubmed IDLast YearTitleAuthors

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

Pathways

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

Protein levels (Protein atlas)

Not detected
Low
Medium
High

References

Pubmed IDYearTitleCitations
179917352008Programmed cell death 4 (PDCD4) is an important functional target of the microRNA miR-21 in breast cancer cells.434
199462722010Negative regulation of TLR4 via targeting of the proinflammatory tumor suppressor PDCD4 by the microRNA miR-21.360
170531472006S6K1- and betaTRCP-mediated degradation of PDCD4 promotes protein translation and cell growth.259
183729202008MicroRNA-21 promotes cell transformation by targeting the programmed cell death 4 gene.242
196332922009Hyaluronan-CD44 interaction with protein kinase C(epsilon) promotes oncogenic signaling by the stem cell marker Nanog and the Production of microRNA-21, leading to down-regulation of the tumor suppressor protein PDCD4, anti-apoptosis, and chemotherapy resistance in breast tumor cells.121
192964682009MicroRNA-21 is overexpressed in human cholangiocarcinoma and regulates programmed cell death 4 and tissue inhibitor of metalloproteinase 3.114
166829502006Involvement of programmed cell death 4 in transforming growth factor-beta1-induced apoptosis in human hepatocellular carcinoma.89
216022712011Identification of novel microRNA signatures linked to human lupus disease activity and pathogenesis: miR-21 regulates aberrant T cell responses through regulation of PDCD4 expression.89
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.81
196411832009Aberrant overexpression of microRNAs activate AKT signaling via down-regulation of tumor suppressors in natural killer-cell lymphoma/leukemia.80

Citation

Nancy H Colburn

PDCD4 (Programmed Cell Death 4)

Atlas Genet Cytogenet Oncol Haematol. 2007-08-01

Online version: http://atlasgeneticsoncology.org/gene/41675/pdcd4