RGD Reference Report - Excess putrescine accumulation inhibits the formation of modified eukaryotic initiation factor 5A (eIF-5A) and induces apoptosis. - Rat Genome Database

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Excess putrescine accumulation inhibits the formation of modified eukaryotic initiation factor 5A (eIF-5A) and induces apoptosis.

Authors: Tome, ME  Fiser, SM  Payne, CM  Gerner, EW 
Citation: Tome ME, etal., Biochem J. 1997 Dec 15;328 ( Pt 3):847-54.
RGD ID: 2308862
Pubmed: PMID:9396730   (View Abstract at PubMed)
PMCID: PMC1218996   (View Article at PubMed Central)

DH23A cells, an alpha-difluoromethylornithine-resistant variant of the parental hepatoma tissue culture cells, express high levels of stable ornithine decarboxylase. Aberrantly high expression of ornithine decarboxylase results in a large accumulation of endogenous putrescine and increased apoptosis in DH23A cells when alpha-difluoromethylornithine is removed from the culture. Treatment of DH23A cells with exogenous putrescine in the presence of alpha-difluoromethylornithine mimics the effect of drug removal, suggesting that putrescine is a causative agent or trigger of apoptosis. Accumulation of excess intracellular putrescine inhibits the formation of hypusine in vivo, a reaction that proceeds by the transfer of the butylamine moiety of spermidine to a lysine residue in eukaryotic initiation factor 5A (eIF-5A). Treatment of DH23A cells with diaminoheptane, a competitive inhibitor of the post-translational modification of eIF-5A, causes both the suppression of eIF-5A modification in vivo and induction of apoptosis. These data support the hypothesis that rapid degradation of ornithine decarboxylase is a protective mechanism to avoid cell toxicity from putrescine accumulation. Further, these data suggest that suppression of modified eIF-5A formation is one mechanism by which cells may be induced to undergo apoptosis.



Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Eif5aRatnegative regulation of apoptotic process  IMP  RGD 

Objects Annotated

Genes (Rattus norvegicus)
Eif5a  (eukaryotic translation initiation factor 5A)


Additional Information