An anti-apoptotic role for the p53 family member, p73, during developmental neuron death.
p53 plays an essential pro-apoptotic role, a function thought to be shared with its family members p73 and p63. Here, we show that p73 is primarily present in developing neurons as a truncated isoform whose levels are dramatically decreased when sympathetic neurons apoptose after nerve growth factor (NGF) withdrawal. Increased expression of truncated p73 rescues these neurons from apoptosis induced by NGF withdrawal or p53 overexpression. In p73-/- mice, all isoforms of p73 are deleted and the apoptosis of developing sympathetic neurons is greatly enhanced. Thus, truncated p73 is an essential anti-apoptotic protein in neurons, serving to counteract the pro-apoptotic function of p53.
Pozniak
C D
CD
Center for Neuronal Survival, Brain Tumor Research Center, Montreal Neurological Institute, McGill University, Montreal, Canada H3A 2B4.
Radinovic
S
S
Yang
A
A
McKeon
F
F
Kaplan
D R
DR
Miller
F D
FD
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000737:chemistry / Q000502:physiology*; D004926:Escherichia coli; D016147:Genes, Tumor Suppressor; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D020932:Nerve Growth Factor / Q000494:pharmacology; D009474:Neurons / Q000502:physiology*; D009687:Nuclear Proteins / Q000096:biosynthesis / Q000737:chemistry / Q000502:physiology*; D020033:Protein Isoforms / Q000096:biosynthesis / Q000737:chemistry / Q000502:physiology; D011994:Recombinant Proteins; D013564:Sympathetic Nervous System / Q000166:cytology / Q000502:physiology*; D000072160:Tumor Protein p73; D016159:Tumor Suppressor Protein p53 / Q000037:antagonists & inhibitors / Q000502:physiology*; D025521:Tumor Suppressor Proteins
D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D020033:Protein Isoforms; D011994:Recombinant Proteins; C000606460:TP73 protein, human; C000606368:Trp73 protein, mouse; D000072160:Tumor Protein p73; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; D020932:Nerve Growth Factor