DUG is a novel homologue of translation initiation factor 4G that binds eIF4A.
To elucidate the molecular mechanisms of cell death, we have cloned a new gene, designated death-upregulated gene (DUG), from rat insulinoma cells. DUG is constitutively expressed at very low levels in normal cells but is dramatically upregulated in apoptotic cells following serum/glucose starvation or death receptor ligation by Fas ligand. The DUG mRNA is present in two splicing forms: a long form that encodes a protein of 469 amino acids and a short form that gives rise to a polypeptide of 432 amino acids. The predicted DUG protein sequence contains two putative nuclear localization signals and multiple phosphorylation sites for protein kinases and two conserved MA3 domains. Importantly, DUG is homologous to eukaryotic translation initiation factor (eIF) 4G and binds to eIF4A presumably through MA3 domains. Upon transfection, DUG inhibits both intrinsic and extrinsic pathways of apoptosis. Thus, DUG is a novel homologue of eIF4G that regulates apoptosis.
Göke
Alexandra
A
Clinical Research Unit, University of Marburg, Baldingerstrasse, D-35033, Marburg, Germany
Göke
Rüdiger
R
Knolle
Anja
A
Trusheim
Heidi
H
Schmidt
Harald
H
Wilmen
Andreas
A
Carmody
Ruaidhri
R
Göke
Burkhard
B
Chen
Youhai H
YH
D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D051017:Apoptosis Regulatory Proteins; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D039601:Eukaryotic Initiation Factor-4A; D039603:Eukaryotic Initiation Factor-4G; D015870:Gene Expression; D008969:Molecular Sequence Data; D010448:Peptide Initiation Factors / Q000737:chemistry / Q000378:metabolism*; D051381:Rats; D014407:Tumor Cells, Cultured; D015854:Up-Regulation
D051017:Apoptosis Regulatory Proteins; D002352:Carrier Proteins; D039603:Eukaryotic Initiation Factor-4G; C467042:Pdcd4 protein, rat; D010448:Peptide Initiation Factors; D039601:Eukaryotic Initiation Factor-4A