Molecular cloning of a novel polypeptide, DP5, induced during programmed neuronal death.
To study the molecular mechanisms underlying neuronal programmed cell death (PCD), we performed differential display screening for genes, the expression of which was induced during PCD in the sympathetic neuron culture model deprived of NGF. We cloned a gene encoding a novel polypeptide (DP5) which consisted of 92 amino acids. DP5 polypeptide had no homology with any other known protein and contained no motif that would indicate its putative biochemical functions. DP5 mRNA levels peaked at 15 h after nerve growth factor withdrawal, concurrent with the time at which neurons were committed to die. The induction of DP5 gene expression was blocked when cell death was rescued by treatment with cycloheximide, KCl, or the cyclic AMP analogue CPTcAMP. Overexpression of the full-length DP5 in cultured sympathetic neurons was in itself sufficient to induce apoptosis. These results suggest that DP5 plays a role in programmed neuronal death.
Imaizumi
K
K
Department of Molecular Neurobiology, "TANABE", Osaka University Medical School, 2-2 Yamadaoka, Suita, Osaka 565, Japan. imaizumi@brain.med.osaka-u.ac.jp
Tsuda
M
M
Imai
Y
Y
Wanaka
A
A
Takagi
T
T
Tohyama
M
M
D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D051017:Apoptosis Regulatory Proteins; D015152:Blotting, Northern; D003001:Cloning, Molecular; D000242:Cyclic AMP / Q000031:analogs & derivatives / Q000494:pharmacology; D003513:Cycloheximide / Q000494:pharmacology; D007163:Immunosorbent Techniques; D008969:Molecular Sequence Data; D009474:Neurons / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D009479:Neuropeptides / Q000096:biosynthesis / Q000235:genetics*; D016366:Open Reading Frames; D016716:PC12 Cells; D011189:Potassium Chloride / Q000494:pharmacology; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015183:Restriction Mapping; D017783:Superior Cervical Ganglion / Q000166:cytology; D013873:Thionucleotides / Q000494:pharmacology; D014018:Tissue Distribution
D051017:Apoptosis Regulatory Proteins; C484585:Hrk protein, rat; D009479:Neuropeptides; D011500:Protein Synthesis Inhibitors; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D013873:Thionucleotides; C015929:8-((4-chlorophenyl)thio)cyclic-3',5'-AMP; D011189:Potassium Chloride; D003513:Cycloheximide; D000242:Cyclic AMP