Ciclo cellulare, riparazione del DNA ed apoptosi.
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Transcript of Ciclo cellulare, riparazione del DNA ed apoptosi.
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Ciclo cellulare, riparazione del DNA
ed apoptosi
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Ciclo cellulare
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Perche' modificare il ciclo cellulare?
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R
cdk4/6
cyclin D
GF
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Figure 8.11b The Biology of Cancer (© Garland Science 2007)
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c-fos
c-jun
c-myc
Id-1
Cyclin D1
Cyclin E
Cyclin A
PCNA
0 1/2 1 2 4 8 16 24Pro
life
rati
ng
my
ob
las
ts
hrs in 10% SERUM
Localizzazione nucleare
Altre modalita’ di regolazione delle cicline D:
Stabilita’/degradazione
Quiescent myoblasts
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Figure 8.10 The Biology of Cancer (© Garland Science 2007)
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G1 S MG2
Il ciclo cellulare
ciclina Ecdk2
ciclina Acdk2
ciclina Dcdk4 o cdk6
ciclina Acdk1
ciclina Bcdk1
Regolato dai fattori di crescita Programma cellulare autonomo
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G1
ciclina Ecdk2ciclina D
cdk4 o cdk6
pRb
E2F
P
La fase G1
Regolato dai fattori di crescita
DNA pol
DNA pol
PCNA
RPA
MCM2-7
etc…
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G1 S MG2
Il ciclo cellulare
ciclina Ecdk2
ciclina Acdk2
ciclina Dcdk4 o cdk6
ciclina Acdk1
ciclina Bcdk1
pRb
PE2F
Pdegradazione
ciclina A
degradazioneciclina B
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Modificata da: Rb and tumorigenesis (Landes Biosciences, 2006)
La via di pRb nei tumori
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Modificata da: The biology of cancer (Garland Science 2007)
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G1 S
ciclina Ecdk2
ciclina Acdk2
ciclina Dcdk4 o cdk6
MG2
ciclina Acdk1
ciclina Bcdk1
I checkpoint del ciclo cellulare
p53p21pRb
controllo di stress edanno al DNA
correttezza della replicazione
completezza dellareplicazione
e assenza di rotture
assemblaggio del fuso e segregazionecromosomica
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Riparazione del DNA
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Trends in Genetics 15:93-94, 1999
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Figure 12.6 The Biology of Cancer (© Garland Science 2007)
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Deaminazione
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Depurinazione
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Ossidazione
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Dimeri di pirimidine
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Formazione diaddotti del DNA
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MAP: Myh-associated polyposis
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Figure 12.23b The Biology of Cancer (© Garland Science 2007)
Xeroderma pigmentosum:altissima incidenza di tumorimaligni della pelle espostaa raggi UV.
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Figure 12.8c The Biology of Cancer (© Garland Science 2007)
Mismatch repair
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Figure 12.8a The Biology of Cancer (© Garland Science 2007)
Mismatch repair
Hereditary non-polyposiscolon cancer (HNPCC).
Difetti del mismatch repairnel 15% dei tumori sporadicidel colon, dello stomaco,dell'ovaio e dell'endometrio.
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Figure 12.32 The Biology of Cancer (© Garland Science 2007)
Homology-directed repair
Difetti di BRCA1 o BRCA2prevengono la riparazione guidatadall'omologia.
Carcinomi della mammella edell'ovaio.
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Figure 12.33 The Biology of Cancer (© Garland Science 2007)
Non-homologous end joining (NHEJ)
Difetto della proteina NBS(nibrina).
Linfomi.
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Modificata da: The biology of cancer (Garland Science 2007)
Instabilita'cromosomica
cellule normali ca. mammario
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Apoptosi
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p53
ipertermiascarsita’ di nucleotidi
radiazioni ionizzanti
oncogeni attivati
ipossia
blocco della trascrizione
Bax Noxa Puma
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pro-apoptoticsignals
anti-apoptoticsignals
Modificata da: The biology of cancer (Garland Science 2007)
Apoptosi intrinseca
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Apoptosi estrinsecaTNF-, FasL, TRAIL
Modificata da: The biology of cancer (Garland Science 2007)
FA
DD
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Apoptosi estrinsecaTNF-, FasL, TRAIL
Modificata da: The biology of cancer (Garland Science 2007)
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Apoptosi estrinsecaTNF-, FasL, TRAIL
Modificata da: The biology of cancer (Garland Science 2007)
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Modificata da Lum et al. Cell 120:237-248, 2005
Autofagia
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Modificata da: The biology of cancer (Garland Science 2007)
Beclin-1 hemizygous inactivation haploinsufficient, suppression of autophagy many types
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