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Symbol PDCD4 contributors: mct/npt/pgu - updated : 20-08-2016
HGNC name programmed cell death 4 (neoplastic transformation inhibitor)
HGNC id 8763
Location 10q25.2      Physical location : 112.631.595 - 112.659.763
Synonym name
  • death upregulated gene
  • programmed cell death 4
  • nuclear antigen H731
  • Synonym symbol(s) H731, DUG, MGC33046, MGC33047
    TYPE functioning gene
    STRUCTURE 28.21 kb     13 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    regulatory sequence Promoter (CAAT box)
    Binding site   transcription factor
    text structure
  • regulation of gene expression via Sp1/Sp3 (Leupold 2007)
  • transcriptional start sites of the promoter, is a functional CCAAT-box
  • ZNF148 is a regulator of PDCD4 by binding to the basal promoter either alone or by interacting with Sp family members
  • MAPPING cloned Y linked N status provisional
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    12 - 3591 51.6 469 - 2013 23578931
    13 - 3675 50.4 458 - 2013 23578931
  • including an alternate in-frame exon in the 5' coding region
  • using a downstream start codon compared to variant 1
  • isoform 2, PDCD4B
  • is a relevant target of MIR21 and protection of PDCD4B from MIR21 binding results in failure of atrioventricular valve development
  • 12 - 3602 - 455 - 2013 23578931
    Type widely
       expressed in (based on citations)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestivepancreas exocrineacinar gland  highly Homo sapiensAdult
    Endocrinepancreasislet of Langerhans  highly Homo sapiens
    Reproductivefemale systembreastmammary gland highly
    SystemCellPubmedSpeciesStageRna symbol
    Endocrineislet cell (alpha,beta...) Homo sapiens
    Urinaryduct cell
    cell lineage
    cell lines highly expressed in bladder carcinoma and breast carcinoma
    at STAGE
  • two putative nuclear localization signals
  • multiple phosphorylation sites for protein kinases
  • two C-terminal MA3 domains, which are thought to be responsible for its inhibitory function, and bind specifically to the eIF4A N-terminal domain
    interspecies homolog to murine Pdcd4 (96.8pc)
    homolog to rattus Pdcd4 (96.8pc)
    intraspecies homolog to EIF4G
  • PDCD4 family
  • CATEGORY regulatory , tumor suppressor
    SUBCELLULAR LOCALIZATION     intracellular
    text overproduced and localized in the cytoplasm during the cell cycle in tumor cell lines
    basic FUNCTION
  • regulating EIF4G-dependent translation through direct interaction with EIF4G and RPS13 in senescent fibroblasts
  • inhibiting the translation initiation factor EIF4A
  • inhibiting tumor promoter-induced neoplastic transformation
  • down-regulating the expression of MAP4K1, thus inhibiting events important in driving invasion, namely, MAPK85 activation and consequent JUN-dependent transcription
  • inhibit invasion by activating activator protein-1 (AP-1)
  • inhibits invasion/intravasation and regulates urokinase receptor PLAUR gene expression via Sp-transcription factors
  • involved in TGFB1-induced apoptosis via the SMAD pathway
  • involved in the regulation of transcription and translation
  • directly involved in translational suppression of a natural mRNA, providing the first evidence for a key role of the RNA-binding domain in targeting PDCD4 to a specific mRNA
  • critical suppressor of apoptosis by inhibiting the translation of procaspase-3 mRNA
  • by affecting the translation and activity of TP53, is likely to exert pleiotropic effects on these biological processes and thereby influence the cellular homeostasis
  • may play a critical function in arresting cell cycle progression at key checkpoint, thus inhibiting cell proliferation, as well as suppressing tumour metastasis
  • CELLULAR PROCESS cell life, proliferation/growth
    cell life, cell death/apoptosis
    a component
  • form a tighter and more stable complex with EIF4A, which explains the need for two tandem MA3 domains
  • NFKB&
  • 8722;MIR21&
    8722;PDCD4 axis plays a crucial role in Type 1 diabetes
    RNA binding
    small molecule
  • binding to EIF4A presumably through MA3 domains and to EIF4G (PDCD4 MA3 domains compete with the eIF4G-MA3 and with RNA for binding to EIF4A)
  • associated with TP53 mRNA and suppresses its translation
  • is a specific repressor of the internal ribosome entry site (IRES)-dependent translation of cellular mRNAs (such as XIAP and BCL2L1) that mediate FGF2-RPS6K2 prosurvival signaling
  • negative correlation between the expression of FAT1 and PDCD4
  • MIR21 plays a necessary role in cardiac valvulogenesis, in large part due to an obligatory downregulation of PDCD4
  • cell & other
    inhibited by IL2 stimulation
    Other phosphorylated by S6K1 in response to mitogens and subsequently degraded via the ubiquitin ligase SCF-beta, allowing efficient proteins synthesis and cell growth
    increased expression by IL12 stimulation
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    loss of expression correlated with tumor progression of lung and colon carcinoma
    tumoral     --low  
    associated with the progression of serous cystadenocarcinomas and may serve as an important prognostic marker
    tumoral     --over  
    in bladder carcinoma and breast carcinoma
    constitutional       loss of function
    deficiency in pancreatic islet beta cells renders them resistant to death
    tumoral     --low  
    significantly lower in moderately or poorly differentiated digestive tract cancers than in well-differentiated cancers
    tumoral     --low  
    in the high malignant group of glioma significantly decreased compared with the low malignant group
    Variant & Polymorphism
    Candidate gene
  • might be a potentially valuable molecular target in diagnosis for human digestive tract cancers
  • Therapy target
    diabetetype 1 
    the NFkB−MIR21−PDCD4 axis plays a crucial role in T1D and represents a unique therapeutic target for treating the disease
    might be a potentially valuable molecular target in therapy for human digestive tract cancers
    may be a new therapeutic target in proliferative vascular diseases
    PDCD5 mRNA expressions is promising target for the diagnosis and treatment of glioma