Neuronal survival and p73/p63/p53: a family affair.
Elucidating the mechanisms that regulate the life versus death of mammalian neurons is important not only for our understanding of the normal biology of the nervous system but also for our efforts to devise approaches to maintain neuronal survival in the face of traumatic injury or neurodegenerative disorders. Here, we review the emerging evidence that a key survival/death checkpoint in both peripheral and central neurons involves the p53 tumor suppressor and its newly discovered family members, p73 and p63. The full-length isoforms of these proteins function as proapoptotic proteins, whereas naturally occurring N-terminal truncated variants of p73 and p63 act as prosurvival proteins, at least partially by antagonizing the full-length family members. The authors propose that together, these isoforms comprise an upstream rheostat that sums different environmental cues to ultimately determine neuronal survival during development, during neuronal maintenance in adult animals, and even following traumatic injury.
Jacobs
W Bradley
WB
Developmental Biology and Cancer Research, Hospital for Sick Children, Division of Neurosurgery, Department of Surgery, University of Toronto, Toronto, Ontario, Canada.
Walsh
Gregory S
GS
Miller
Freda D
FD
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D002470:Cell Survival / Q000502:physiology; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology*; D016147:Genes, Tumor Suppressor; D006801:Humans; D005810:Multigene Family / Q000502:physiology*; D009474:Neurons / Q000166:cytology / Q000502:physiology*; D009687:Nuclear Proteins / Q000235:genetics / Q000502:physiology*; D010750:Phosphoproteins / Q000235:genetics / Q000502:physiology*; D020033:Protein Isoforms / Q000235:genetics / Q000502:physiology; D015534:Trans-Activators / Q000235:genetics / Q000502:physiology*; D014157:Transcription Factors; D000072160:Tumor Protein p73; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000502:physiology*; D025521:Tumor Suppressor Proteins
D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D010750:Phosphoproteins; D020033:Protein Isoforms; C115051:TP63 protein, human; C000606460:TP73 protein, human; D015534:Trans-Activators; D014157:Transcription Factors; D000072160:Tumor Protein p73; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins