p73-induced apoptosis: a question of compartments and cooperation.
The transcriptionally active forms of p73 are capable of inducing apoptosis, and the isoforms termed TAp73 are important players when E2F and its oncogenic activators induce programmed cell death. However, the conditions under that TAp73 can kill a cell remain to be clarified. Recently, it has been found that p73 proteins are not merely floating in the nucleoplasm but rather can associate with specific compartments in the cell. Examples of intranuclear compartments associated with p73 proteins include the PML oncogenic domains and the nuclear matrix. In addition, p73 is found in the cytoplasm. It remains to be seen whether p73 might also associate with mitochondria, in analogy with p53. The relocalization of p73 is expected to be mediated by specific binding partners, mostly other proteins. Here, we discuss the possibility that the compartmentalization of p73, and the cooperation with the corresponding binding partners, might decide about its apoptosis-inducing activity.
Dobbelstein
Matthias
M
Institute of Molecular Biology, University of Southern Denmark, Winsløwparken 25, 5000 Odense C, Denmark.
Strano
Sabrina
S
Roth
Judith
J
Blandino
Giovanni
G
D000123:Acetyltransferases / Q000502:physiology; D048868:Adaptor Proteins, Signal Transducing / Q000502:physiology; D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D002352:Carrier Proteins / Q000502:physiology; D002451:Cell Compartmentation / Q000502:physiology*; D018797:Cell Cycle Proteins / Q000502:physiology; D004268:DNA-Binding Proteins / Q000502:physiology*; D016147:Genes, Tumor Suppressor / Q000502:physiology*; D051548:Histone Acetyltransferases; D006801:Humans; D000072340:NIMA-Interacting Peptidylprolyl Isomerase; D009687:Nuclear Proteins / Q000502:physiology*; D019696:Peptidylprolyl Isomerase / Q000502:physiology; D010750:Phosphoproteins / Q000502:physiology; D020033:Protein Isoforms / Q000502:physiology; D016315:Proto-Oncogene Proteins c-abl / Q000502:physiology; D015534:Trans-Activators / Q000502:physiology; D014157:Transcription Factors / Q000502:physiology; D000072160:Tumor Protein p73; D016159:Tumor Suppressor Protein p53 / Q000502:physiology; D025521:Tumor Suppressor Proteins; D000091102:YAP-Signaling Proteins; D050880:p300-CBP Transcription Factors; D000099224:p300-CBP-Associated Factor
D000123:Acetyltransferases; D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D051548:Histone Acetyltransferases; D000072340:NIMA-Interacting Peptidylprolyl Isomerase; D009687:Nuclear Proteins; D019696:Peptidylprolyl Isomerase; D010750:Phosphoproteins; D020033:Protein Isoforms; D016315:Proto-Oncogene Proteins c-abl; D015534:Trans-Activators; D014157:Transcription Factors; D000072160:Tumor Protein p73; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; D000091102:YAP-Signaling Proteins; D050880:p300-CBP Transcription Factors; D000099224:p300-CBP-Associated Factor; C115051:TP63 protein, human; C000606460:TP73 protein, human; C000606368:Trp73 protein, mouse; C486223:Yap1 protein, mouse; C000606846:PIN1 protein, human; C000606850:Pin1 protein, mouse