5 hrs

1
Do p63 and p73 play a role in the DNA damage
response in vivo?
5 hrs
Pregnant p63/-p73/- females day 13.5
2
Do p63 and p73 play a role in the DNA damage
response in vivo?
E. Flores et al., Nature, 2002
3
p21 and mdm2 are induced in the brain of
p63-/-p73-/- embryos upon treatment with
g-irradiation
E. Flores et al., Nature, 2002
4
PERP and bax are not induced in the brain of
p63-/-p73-/- embryos upon treatment with
g-irradiation
E. Flores et al., Nature, 2002
5
Chromatin Immunoprecipitation
(ChIP)
6
ChIP analysis of p53 target genes
mdm2
p21
bax
PERP C
NOXA
E. Flores et al., Nature, 2002
7
ChIP analysis of p53 target genes
mdm2
p21
bax
PERP C
NOXA
E. Flores et al., Nature, 2002
8
p53
p53
Growth Arrest Genes
p53
Apoptosis Genes
9
p53
p53
Growth Arrest Genes
Apoptosis Genes
E. Flores et al., Nature, 2002
10
DNA damage and the p53 family network
p19
p53
mdm2
p63
p73
p21, GADD45
Bax, PERP, NOXA
Growth Arrest
Apoptosis
11
Roles for p63 and p73 in tumor suppression?
p63
?
p73
?
p53
Tumor Prone
12
Are p63 and/or p73 involved in tumor suppression?
p73/-
p63/-
p73/-
p63/-
vs.
vs.
p73/-
p53/-
p53/-
p63/-
p53/-
vs.
vs.
13
Are p63 and/or p73 involved in tumor suppression?
p73/-
p63/-
p73/-
p63/-
vs.
vs.
14
p63 p73 Heterozygous Mice Are Tumor Prone
p63/-
lung adenoma
squamous cell hyperplasia
squamous cell carcinoma
sarcomas
15
p63 p73 Heterozygous Mice Are Tumor Prone
lung adenoma
squamous cell hyperplasia
p73/-
thymic lymphoma
sarcomas
16
p63 p73 Heterozygous Mice Are Tumor Prone
p63/-
p63/-p73/-
squamous cell hyperplasia
lung adenocarcinoma
squamous cell carcinoma
p73/-
mammary adenocarcinoma
sarcomas
thymic lymphoma
17
Tumor Spectrum of p63/-p73/- mice
E. Flores et al., Cancer Cell, April, 2005
18
Tumor Spectrum of p63/-p73/- mice
Squamous Cell Carcinoma
p63/-p73/-
30
E. Flores et al., Cancer Cell, April, 2005
19
Are p63 and/or p73 involved in tumor suppression?
p73/-
p53/-
p53/-
p63/-
p53/-
vs.
vs.
20
p53 Family Compound Mutants Develop Complex Tumor
Spectra
sarcomas
thymic lymphoma