Abstract
The complexity of the p53 protein, coupled with the vast cellular responses to p53, is simply astonishing. As new isoforms, functional domains and protein–protein interactions are described; each morsel of information forces us to think (and re-think) about how it ‘fits’ into the current p53 paradigm. One aspect of p53 signaling that is under refinement is the mechanism(s) leading to apoptosis. Here we discuss what is known about p53-induced apoptosis, what proteins and protein–protein interactions are responsible for regulating apoptosis, how can this cascade be genetically dissected, and what pharmacological tools are available to modulate p53-dependent apoptosis. While everything may not comfortably fit into our understanding of p53, all of these data will certainly broaden our viewpoint on the complexity and significance of the p53-induced apoptotic pathway. Here, our discussion is primarily focused on the works presented at the 12th International p53 Workshop, except where appropriate background is required.
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Abbreviations
- APAF1:
-
apoptotic protease activating factor 1
- ASPP:
-
ankyrin repeat, SH3 domain and proline-rich domain containing proteins/apoptosis stimulating proteins of p53
- BAK:
-
Bcl-2 antagonist/killer
- BAX:
-
Bcl-2-associated X protein
- BH3:
-
Bcl-2-homology domain-3
- BID:
-
BH3-interacting-domain
- ced-3 :
-
Caenorhabditis elegans cell-death abnormality-3
- C9DN:
-
dominant-negative caspase-9
- CHC:
-
clathrin heavy chain
- FADD:
-
FAS-associated death domain
- HIPK2:
-
homeodomain-interacting protein kinase 2
- iASPP:
-
inhibitor of ASPP1/2
- ICE:
-
interleukin-1 converting enzyme
- MCL-1:
-
myeloid cell leukemia-1
- MOMP:
-
mitochondrial outer-membrane permeabilization
- p53 QS :
-
L25Q, W26S Trp53 knock-in
- PIDD :
-
p53-indicible death domain
- PRIMA-1:
-
p53 reactivation and induction of massive apoptosis
- PUMA:
-
p53-upregulated modulator of apoptosis
- RITA:
-
reactivation of p53 and induction of tumor cell apoptosis
- tBID:
-
truncated BID
- TNF:
-
tumor necrosis factor
- TNFR1:
-
TNF receptor 1
- TRADD:
-
TNFR1-associated death domain
- TUNEL:
-
terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling
- YB1:
-
Y-box binding protein-1
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Chipuk, J., Green, D. Dissecting p53-dependent apoptosis. Cell Death Differ 13, 994–1002 (2006). https://doi.org/10.1038/sj.cdd.4401908
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DOI: https://doi.org/10.1038/sj.cdd.4401908
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