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GENETIC BASIS
OF
CANCER
Tumor suppressor gene p53
@PIYUSH.R.SHARMA
• Cancer – a large group of diseases
characterized by the uncontrolled growth
and spread of abnormal cells.
• All cancers derive from single cells that
have acquired the characteristics
continually dividing in an unrestrained
manner and invading surrounding tissues.
@PIYUSH.R.SHARMA
Tumor Suppressor Gene - p53
• Protein 53
• TRP 53 – Transformation Related Protein 53
• TP 53 – Tumor Protein 53
• Master Watchman
• Guardian Of Genome
present in nucleus of all the cells on the short arm
of the chromosome 17
@PIYUSH.R.SHARMA
Tumor Suppressor Gene - p53
DNA Binding
domain
{Arg rich}
Tetramerization
domain
Tetramerization
domain
Protein
rich
region
Regulatory
domain
{Lys rich}
142 aa 61-94 aa 102-292 aa 324-355 aa 363-393 aa
N C
CENTRAL
CORE
DOMAIN
STRUCTURE
@PIYUSH.R.SHARMA
 Provides p21
 provides GADD 45
 Provides 14-3.3 ϭ
 Provides p53R2
p53
MDM 2
Ub
Case 1 – Normal Cell
Case 2 – Abnormal Cell
ATM
DNA damage
ATR
CHK
1 OR 2
Nucleus
P
CHK
1 OR 2
P
USP 7
p53
P
@PIYUSH.R.SHARMA
Biological Importance
 It is present in the nucleus of all the cells.
 It activates the genes for DNA repair.
 It also activates the genes for apoptosis like NOXA,PUMA,BAX.
 If a person inherits a single copy of functional p53 than it is
predisposed to number of independent tumors.
 It is a tumor suppressor gene because develops cell cycle arrest
at multiple check points and not allow the cell with DNA breaks to
move into next phase of cell cycle.
 The p53 prevents the occurrence of mutations and promotes
genomic stability so known as Guardian Of Genome.
 If in vitro p53 is provided to p53 deficient cell than it has been
shown to cause the apoptosis of damage cells.
@PIYUSH.R.SHARMA
Any questions
GENETIC BASIS
OF
CANCER
@PIYUSH.R.SHARMA
Thank you
……………………
……………………
@PIYUSH.R.SHARMA

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Cancer biology (Protein-53 Tumor suppressor gene)

  • 1. GENETIC BASIS OF CANCER Tumor suppressor gene p53 @PIYUSH.R.SHARMA
  • 2. • Cancer – a large group of diseases characterized by the uncontrolled growth and spread of abnormal cells. • All cancers derive from single cells that have acquired the characteristics continually dividing in an unrestrained manner and invading surrounding tissues. @PIYUSH.R.SHARMA
  • 3. Tumor Suppressor Gene - p53 • Protein 53 • TRP 53 – Transformation Related Protein 53 • TP 53 – Tumor Protein 53 • Master Watchman • Guardian Of Genome present in nucleus of all the cells on the short arm of the chromosome 17 @PIYUSH.R.SHARMA
  • 4. Tumor Suppressor Gene - p53 DNA Binding domain {Arg rich} Tetramerization domain Tetramerization domain Protein rich region Regulatory domain {Lys rich} 142 aa 61-94 aa 102-292 aa 324-355 aa 363-393 aa N C CENTRAL CORE DOMAIN STRUCTURE @PIYUSH.R.SHARMA
  • 5.  Provides p21  provides GADD 45  Provides 14-3.3 ϭ  Provides p53R2 p53 MDM 2 Ub Case 1 – Normal Cell Case 2 – Abnormal Cell ATM DNA damage ATR CHK 1 OR 2 Nucleus P CHK 1 OR 2 P USP 7 p53 P @PIYUSH.R.SHARMA
  • 6. Biological Importance  It is present in the nucleus of all the cells.  It activates the genes for DNA repair.  It also activates the genes for apoptosis like NOXA,PUMA,BAX.  If a person inherits a single copy of functional p53 than it is predisposed to number of independent tumors.  It is a tumor suppressor gene because develops cell cycle arrest at multiple check points and not allow the cell with DNA breaks to move into next phase of cell cycle.  The p53 prevents the occurrence of mutations and promotes genomic stability so known as Guardian Of Genome.  If in vitro p53 is provided to p53 deficient cell than it has been shown to cause the apoptosis of damage cells. @PIYUSH.R.SHARMA

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