PDCD4 (Programmed Cell Death 4)
2007-08-01 Nancy H Colburn AffiliationLaboratory of Cancer Prevention, National Cancer Institute, Bldg. 576, Rm. 101, Frederick, MD 21702-1201, USA
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
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 ID | Last Year | Title | Authors |
|---|---|---|---|
| 12082539 | 2002 | Targeted disruption of c-myb in the chicken pre B-cell line DT40. | Appl H et al |
| 9759869 | 1998 | 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 et al |
| 12894233 | 2003 | The transformation suppressor protein Pdcd4 shuttles between nucleus and cytoplasm and binds RNA. | Böhm M et al |
| 12898601 | 2003 | Loss of PDCD4 expression in human lung cancer correlates with tumour progression and prognosis. | Chen Y et al |
| 10570194 | 1999 | Differentially expressed protein Pdcd4 inhibits tumor promoter-induced neoplastic transformation. | Cmarik JL et al |
| 17053147 | 2006 | S6K1- and betaTRCP-mediated degradation of PDCD4 promotes protein translation and cell growth. | Dorrello NV et al |
| 17114484 | 2006 | Translational regulation of autoimmune inflammation and lymphoma genesis by programmed cell death 4. | Hilliard A et al |
| 16024603 | 2005 | Epidermal expression of the translation inhibitor programmed cell death 4 suppresses tumorigenesis. | Jansen AP et al |
| 16648576 | 2006 | 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 et al |
| 17060447 | 2007 | Structural basis for inhibition of translation by the tumor suppressor Pdcd4. | LaRonde-LeBlanc N et al |
| 17297470 | 2007 | Tumor suppressor Pdcd4 inhibits invasion/intravasation and regulates urokinase receptor (u-PAR) gene expression via Sp-transcription factors. | Leupold JH et al |
| 17259349 | 2007 | Programmed cell death-4 tumor suppressor protein contributes to retinoic acid-induced terminal granulocytic differentiation of human myeloid leukemia cells. | Ozpolat B et al |
| 16357133 | 2005 | Akt phosphorylates and regulates Pdcd4 tumor suppressor protein. | Palamarchuk A et al |
| 11313950 | 2001 | The chicken Pdcd4 gene is regulated by v-Myb. | Schlichter U et al |
| 17053135 | 2006 | Signal transduction. Protein synthesis and oncogenesis meet again. | Sonenberg N et al |
| 17310995 | 2007 | Structure of the C-terminal MA-3 domain of the tumour suppressor protein Pdcd4 and characterization of its interaction with eIF4A. | Waters LC et al |
| 15082783 | 2004 | 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 et al |
| 12482958 | 2003 | The transformation suppressor Pdcd4 is a novel eukaryotic translation initiation factor 4A binding protein that inhibits translation. | Yang HS et al |
| 12802278 | 2003 | Pdcd4 suppresses tumor phenotype in JB6 cells by inhibiting AP-1 transactivation. | Yang HS et al |
| 16449643 | 2006 | Tumorigenesis suppressor Pdcd4 down-regulates mitogen-activated protein kinase kinase kinase kinase 1 expression to suppress colon carcinoma cell invasion. | Yang HS et al |
| 12524209 | 2003 | Promising molecular targets for cancer prevention: AP-1, NF-kappa B and Pdcd4. | Young MR et al |
| 16682950 | 2006 | Involvement of programmed cell death 4 in transforming growth factor-beta1-induced apoptosis in human hepatocellular carcinoma. | Zhang H et al |
| 11494140 | 2001 | Detection 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 ID | Transcript ID | Uniprot |
|---|---|---|
| ENSG00000150593 | ENST00000280154 | Q53EL6 |
| ENSG00000150593 | ENST00000393104 | Q53EL6 |
| ENSG00000150593 | ENST00000444997 | Q5VZS7 |
Expression (GTEx)
Pathways
| Pathway | Source | External ID |
|---|---|---|
| Proteoglycans in cancer | KEGG | hsa05205 |
| Proteoglycans in cancer | KEGG | ko05205 |
| MicroRNAs in cancer | KEGG | hsa05206 |
| MicroRNAs in cancer | KEGG | ko05206 |
Protein levels (Protein atlas)
References
| Pubmed ID | Year | Title | Citations |
|---|---|---|---|
| 38253901 | 2024 | MicroRNA-181b-5p Facilitates Thyroid Cancer Growth via Targeting Programmed Cell Death 4. | 0 |
| 38293973 | 2024 | [PDCD4 knockdown ameliorates lipopolysaccharide-induced endothelial cell damage by improving mitochondrial dynamics]. | 0 |
| 38324980 | 2024 | PDCD4 deficiency improved 4-vinylcyclohexene dioxide-induced mouse premature ovarian insufficiency. | 0 |
| 38632092 | 2024 | Progress on the relationship between tumor suppressor PDCD4 and diseases based on the analysis of structural characteristics. | 0 |
| 38640981 | 2024 | STAT1 mediated downregulation of the tumor suppressor gene PDCD4, is driven by the atypical cadherin FAT1, in glioblastoma. | 0 |
| 38253901 | 2024 | MicroRNA-181b-5p Facilitates Thyroid Cancer Growth via Targeting Programmed Cell Death 4. | 0 |
| 38293973 | 2024 | [PDCD4 knockdown ameliorates lipopolysaccharide-induced endothelial cell damage by improving mitochondrial dynamics]. | 0 |
| 38324980 | 2024 | PDCD4 deficiency improved 4-vinylcyclohexene dioxide-induced mouse premature ovarian insufficiency. | 0 |
| 38632092 | 2024 | Progress on the relationship between tumor suppressor PDCD4 and diseases based on the analysis of structural characteristics. | 0 |
| 38640981 | 2024 | STAT1 mediated downregulation of the tumor suppressor gene PDCD4, is driven by the atypical cadherin FAT1, in glioblastoma. | 0 |
| 36366842 | 2023 | Gastric Cancer Growth Modulated by circSNTB2/miR-6938-5p/G0S2 and PDCD4. | 0 |
| 36522523 | 2023 | Induction 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 |
| 36826085 | 2023 | Tumor Suppressor p53 Down-Regulates Programmed Cell Death Protein 4 (PDCD4) Expression. | 2 |
| 37088278 | 2023 | Upregulated MicroRNA-21 Drives the Proliferation of Lymphatic Malformation Endothelial Cells by Inhibiting PDCD4. | 0 |
| 37308277 | 2023 | MiR-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/pdcd4
