Proteomic analysis of ubiquitin-proteasome effects: insight into the function of eukaryotic initiation factor 5A.
Oncogene
; 22(31): 4819-30, 2003 Jul 31.
Article
em En
| MEDLINE
| ID: mdl-12894223
ABSTRACT
The global effect of ubiquitin-proteasome (UP) inhibitors on leukemic cell proteome was analysed. A total of 39 protein spots, affected by UP inhibitors, were identified, including 11 new apoptosis-associated proteins. They are involved in different cellular functions and four were associated with caspase-3 activation. Eukaryotic initiation factor 5A (eIF-5A) was identified in two spots; however, the peptide mass-fingerprinting for the accumulated one included a peptide with lysine50, indicating that hypusine formation was suppressed during UP inhibitor-induced apoptosis. Hypusine modification ensues immediately following translation of eIF-5A precursor, unless cells are treated with the modification inhibitors diaminoheptane. However, UP inhibitors induced a much stronger accumulation of unmodified eIF-5A compared to the effect of diaminoheptane. We further showed the unmodified eIF-5A was regulated in a proteasome-dependent manner. Inhibition of hypusine formation by diaminoheptane triggered apoptosis, but of particular interest is the finding that eIF-5A expression inhibition by antisense oligodeoxynucleotides significantly enhanced the stimulating effect of GM-CSF on cell growth. Therefore, the eIF-5A accumulation played important roles in the apoptosis induced by UP inhibitors. Moreover, hypusine inhibition in apoptosis was further revealed to be associated with the subcellular localization of eIF-5A. Our data pave the way to a better understanding of the mechanisms by which UP system has been linked to apoptosis.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Inibidores de Proteases
/
Acetilcisteína
/
Cisteína Endopeptidases
/
Fatores de Iniciação de Peptídeos
/
Regulação da Expressão Gênica
/
Proteínas de Ligação a RNA
/
Perfilação da Expressão Gênica
/
Ubiquitina
/
Leupeptinas
/
Lisina
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
Oncogene
Assunto da revista:
BIOLOGIA MOLECULAR
/
NEOPLASIAS
Ano de publicação:
2003
Tipo de documento:
Article
País de afiliação:
China