Up-regulation of PDCD4 in senescent human diploid fibroblasts.
Programmed cell death 4 (PDCD4) has a common MI domain sharing with death associated protein 5 (DAP5) and a component of eukaryotic translation initiation factor (eIF4G) complex and it might also work as a tumor suppressor. We could find that the message and product of Pdcd4 gene were up-regulated in senescent human diploid fibroblasts. In yeast two hybrid analysis, the C-terminal region of PDCD4 interacted with ribosomal protein S13 (RPS13), ribosomal protein L5 (RPL5), and TI-227H. In in vitro binding assay, RPS13, a component of 40S ribosome was stably bound to PDCD4. We also found that PDCD4 was localized to polysome fractions. We could pull out eIF4G with GST-PDCD4, but eIF4E did not interact with PDCD4. From these results, we could assume that PDCD4 might regulate the eIF4G-dependent translation through direct interactions with eIF4G and RPS13 in senescent fibroblasts.
Kang
Min-Ji
MJ
Department of Biochemistry and Molecular Biology and Ilchun Molecular Medicine Institute, Seoul National University College of Medicine, 28 Yongondong, Chongnogu, Seoul 110-799, Republic of Korea.
Ahn
Hye-Sung
HS
Lee
Ji-Young
JY
Matsuhashi
Sachiko
S
Park
Woong-Yang
WY
D000818:Animals; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins; D002478:Cells, Cultured; D016922:Cellular Senescence / Q000502:physiology*; D003513:Cycloheximide / Q000494:pharmacology; D039603:Eukaryotic Initiation Factor-4G; D005347:Fibroblasts / Q000502:physiology*; D005786:Gene Expression Regulation / Q000502:physiology*; D006367:HeLa Cells; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D010448:Peptide Initiation Factors / Q000378:metabolism; D011132:Polyribosomes / Q000378:metabolism; D011506:Proteins / Q000235:genetics* / Q000378:metabolism; D016601:RNA-Binding Proteins; D011817:Rabbits; D011994:Recombinant Proteins / Q000378:metabolism; D012269:Ribosomal Proteins / Q000378:metabolism; D012879:Skin Physiological Phenomena
D051017:Apoptosis Regulatory Proteins; D039603:Eukaryotic Initiation Factor-4G; C114487:PDCD4 protein, human; D010448:Peptide Initiation Factors; D011506:Proteins; D016601:RNA-Binding Proteins; D011994:Recombinant Proteins; D012269:Ribosomal Proteins; C045454:ribosomal protein S11; D003513:Cycloheximide