Acknowledgements
This work was supported by the ISCRA-CINECA HPC Grants
(HP10BLFPW4 and HP10C8LO8N) and the EU-PRACE DECI
project DyNet. I would like to thank Matteo Lambrughi for fruitful
inputs in the writing of this protocol.
References
1. Zhang Y, Lozano G (2017) p53: multiple
facets of a rubik’s cube. Annu Rev Cancer
Biol 1:185–201. https://doi.org/10.1146/
annurev-cancerbio-050216-121926
2. Vousden KH, Prives C (2009) Blinded by the
light: the growing complexity of p53. Cell
137:413–431
3. Vogelstein B, Lane D, Levine AJ (2000) Surfing the p53 network. Nature 408:307–310
4. Aylon Y, Oren M (2016) The paradox of p53:
what, how, and why? Cold Spring Harb Perspect Med 6(10):a026328
5. Fischer M (2017) Census and evaluation of
p53 target genes. Oncogene 36:3943–3956
6. Luo Q, Beaver JM, Liu Y et al (2017) Dynamics of p53: a master decider of cell fate. Genes
8:66
7. White E (2016) Autophagy and p53. Cold
Spring Harb Perspect Med 6:1–10
8. Pant V, Lozano G (2014) Limiting the power
of p53 through the ubiquitin proteasome
pathway. Genes Dev 28:1739–1751
9. Kandoth C, McLellan MD, Vandin F et al
(2013) Mutational landscape and significance
across 12 major cancer types. Nature
502:333–339
10. Leroy B, Anderson M, Soussi T (2014) TP53
mutations in human cancer: database reassessment and prospects for the next decade. Hum
Mutat 35:672–688
11. Brosh R, Rotter V (2009) When mutants gain
new powers: news from the mutant p53 field.
Nat Rev Cancer 9:701–713
12. Joerger AC, Fersht AR (2016) The p53 pathway: origins, inactivation in cancer, and
emerging therapeutic approaches. Annu Rev
Biochem 85:375–404. https://doi.org/10.
1146/annurev-biochem-060815-014710
13. Wasylishen AR, Lozano G (2016) Attenuating the p53 pathway in human cancers: many
means to the same end. Cold Spring Harb
Perspect Med 6(8):a026211
14. Lambrughi M, De Gioia L, Gervasio FL et al
(2016) DNA-binding protects p53 from
interactions with cofactors involved in
transcription-independent functions. Nucleic
Acids Res 44:9096–9109
15. Green DR, Kroemer G (2009) Cytoplasmic
functions of the tumour suppressor p53.
Nature 458:1127–1130
16. Speidel D (2010) Transcription-independent
p53 apoptosis: an alternative route to death.
Trends Cell Biol 20:14–24
17. Tasdemir E, Maiuri MC, Galluzzi L et al
(2008) Regulation of autophagy by cytoplasmic p53. Nat Cell Biol 10:676–687
18. Vaseva AV, Moll UM (2009) The mitochondrial p53 pathway. Biochim Biophys Acta
Bioenerg 1787:414–420
19. Kokontis JM, Wagner AJ, O’Leary M et al
(2001) A transcriptional activation function
of p53 is dispensable for and inhibitory of its
apoptotic function. Oncogene 20:659–668
20. Leu JI-J, Dumont P, Hafey M et al (2004)
Mitochondrial p53 activates Bak and causes
disruption of a Bak–Mcl1 complex. Nat Cell
Biol 6:443–450
21. Chipuk JE, Green DR (2008) How do BCL-2
proteins induce mitochondrial outer membrane permeabilization? Trends Cell Biol
18:157–164
22. Follis AV, Llambi F, Ou L et al (2014) The
DNA-binding domain mediates both nuclear
and cytosolic functions of p53. Nat Struct
Mol Biol 21:535–543
23. Zhang X, Li CF, Zhang L et al (2016) TRAF6
restricts p53 mitochondrial translocation,
apoptosis, and tumor suppression. Mol Cell
64:803–814
24. Giorgi C, Bonora M, Sorrentino G et al
(2015) p53 at the endoplasmic reticulum regulates apoptosis in a Ca
2+ Àdependent manner. Proc Natl Acad Sci 112:1779–1784
25. Kroemer G, Bravo-San Pedro JM, Galluzzi L
(2015) Novel function of cytoplasmic p53 at
the interface between mitochondria and the
endoplasmic reticulum. Cell Death Dis 6:
e1698
26. Joerger AC, Fersht AR (2007) Structural
biology of the tumor suppressor p53 and
240
Elena Papaleo
This work was supported by the ISCRA-CINECA HPC Grants
(HP10BLFPW4 and HP10C8LO8N) and the EU-PRACE DECI
project DyNet. I would like to thank Matteo Lambrughi for fruitful
inputs in the writing of this protocol.
References
1. Zhang Y, Lozano G (2017) p53: multiple
facets of a rubik’s cube. Annu Rev Cancer
Biol 1:185–201. https://doi.org/10.1146/
annurev-cancerbio-050216-121926
2. Vousden KH, Prives C (2009) Blinded by the
light: the growing complexity of p53. Cell
137:413–431
3. Vogelstein B, Lane D, Levine AJ (2000) Surfing the p53 network. Nature 408:307–310
4. Aylon Y, Oren M (2016) The paradox of p53:
what, how, and why? Cold Spring Harb Perspect Med 6(10):a026328
5. Fischer M (2017) Census and evaluation of
p53 target genes. Oncogene 36:3943–3956
6. Luo Q, Beaver JM, Liu Y et al (2017) Dynamics of p53: a master decider of cell fate. Genes
8:66
7. White E (2016) Autophagy and p53. Cold
Spring Harb Perspect Med 6:1–10
8. Pant V, Lozano G (2014) Limiting the power
of p53 through the ubiquitin proteasome
pathway. Genes Dev 28:1739–1751
9. Kandoth C, McLellan MD, Vandin F et al
(2013) Mutational landscape and significance
across 12 major cancer types. Nature
502:333–339
10. Leroy B, Anderson M, Soussi T (2014) TP53
mutations in human cancer: database reassessment and prospects for the next decade. Hum
Mutat 35:672–688
11. Brosh R, Rotter V (2009) When mutants gain
new powers: news from the mutant p53 field.
Nat Rev Cancer 9:701–713
12. Joerger AC, Fersht AR (2016) The p53 pathway: origins, inactivation in cancer, and
emerging therapeutic approaches. Annu Rev
Biochem 85:375–404. https://doi.org/10.
1146/annurev-biochem-060815-014710
13. Wasylishen AR, Lozano G (2016) Attenuating the p53 pathway in human cancers: many
means to the same end. Cold Spring Harb
Perspect Med 6(8):a026211
14. Lambrughi M, De Gioia L, Gervasio FL et al
(2016) DNA-binding protects p53 from
interactions with cofactors involved in
transcription-independent functions. Nucleic
Acids Res 44:9096–9109
15. Green DR, Kroemer G (2009) Cytoplasmic
functions of the tumour suppressor p53.
Nature 458:1127–1130
16. Speidel D (2010) Transcription-independent
p53 apoptosis: an alternative route to death.
Trends Cell Biol 20:14–24
17. Tasdemir E, Maiuri MC, Galluzzi L et al
(2008) Regulation of autophagy by cytoplasmic p53. Nat Cell Biol 10:676–687
18. Vaseva AV, Moll UM (2009) The mitochondrial p53 pathway. Biochim Biophys Acta
Bioenerg 1787:414–420
19. Kokontis JM, Wagner AJ, O’Leary M et al
(2001) A transcriptional activation function
of p53 is dispensable for and inhibitory of its
apoptotic function. Oncogene 20:659–668
20. Leu JI-J, Dumont P, Hafey M et al (2004)
Mitochondrial p53 activates Bak and causes
disruption of a Bak–Mcl1 complex. Nat Cell
Biol 6:443–450
21. Chipuk JE, Green DR (2008) How do BCL-2
proteins induce mitochondrial outer membrane permeabilization? Trends Cell Biol
18:157–164
22. Follis AV, Llambi F, Ou L et al (2014) The
DNA-binding domain mediates both nuclear
and cytosolic functions of p53. Nat Struct
Mol Biol 21:535–543
23. Zhang X, Li CF, Zhang L et al (2016) TRAF6
restricts p53 mitochondrial translocation,
apoptosis, and tumor suppression. Mol Cell
64:803–814
24. Giorgi C, Bonora M, Sorrentino G et al
(2015) p53 at the endoplasmic reticulum regulates apoptosis in a Ca
2+ Àdependent manner. Proc Natl Acad Sci 112:1779–1784
25. Kroemer G, Bravo-San Pedro JM, Galluzzi L
(2015) Novel function of cytoplasmic p53 at
the interface between mitochondria and the
endoplasmic reticulum. Cell Death Dis 6:
e1698
26. Joerger AC, Fersht AR (2007) Structural
biology of the tumor suppressor p53 and
240
Elena Papaleo