Viral proteins E1B19K and p35 protect sympathetic neurons from cell death induced by NGF deprivation.
To study molecular mechanisms underlying neuronal cell death, we have used sympathetic neurons from superior cervical ganglia which undergo programmed cell death when deprived of nerve growth factor. These neurons have been microinjected with expression vectors containing cDNAs encoding selected proteins to test their regulatory influence over cell death. Using this procedure, we have shown previously that sympathetic neurons can be protected from NGF deprivation by the protooncogene Bcl-2. We now report that the E1B19K protein from adenovirus and the p35 protein from baculovirus also rescue neurons. Other adenoviral proteins, E1A and E1B55K, have no effect on neuronal survival. E1B55K, known to block apoptosis mediated by p53 in proliferative cells, failed to rescue sympathetic neurons suggesting that p53 is not involved in neuronal death induced by NGF deprivation. E1B19K and p35 were also coinjected with Bcl-Xs which blocks Bcl-2 function in lymphoid cells. Although Bcl-Xs blocked the ability of Bcl-2 to rescue neurons, it had no effect on survival that was dependent upon expression of E1B19K or p35.
Martinou
I
I
Glaxo Institute for Molecular Biology, Geneva, Switzerland.
Fernandez
P A
PA
Missotten
M
M
White
E
E
Allet
B
B
Sadoul
R
R
Martinou
J C
JC
D017500:Adenovirus E1A Proteins / Q000096:biosynthesis / Q000378:metabolism; D017501:Adenovirus E1B Proteins / Q000096:biosynthesis / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D001483:Base Sequence; D016923:Cell Death / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D017931:DNA Primers; D019204:GTP-Binding Proteins / Q000502:physiology; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins; D008845:Microinjections; D008969:Molecular Sequence Data; D009414:Nerve Growth Factors / Q000494:pharmacology*; D009474:Neurons / Q000166:cytology* / Q000187:drug effects / Q000502:physiology; D010957:Plasmids; D016133:Polymerase Chain Reaction; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis / Q000502:physiology; D019253:Proto-Oncogene Proteins c-bcl-2; D051381:Rats; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000378:metabolism; D017783:Superior Cervical Ganglion / Q000166:cytology*; D014162:Transfection; D014764:Viral Proteins / Q000096:biosynthesis / Q000378:metabolism*
D017500:Adenovirus E1A Proteins; D017501:Adenovirus E1B Proteins; D017931:DNA Primers; D051034:Inhibitor of Apoptosis Proteins; D009414:Nerve Growth Factors; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D011994:Recombinant Proteins; D014764:Viral Proteins; C086430:inhibitor of apoptosis, Nucleopolyhedrovirus; D019204:GTP-Binding Proteins