Introduction History Tumor suppressor gene- pRB - RB gene - Role of RB in regulation of cell cycle - Tumor associated with RB gene mutation Tumor suppressor gene- p53 - What is p53 gene? - Function of p53 gene - How it regulates cell cycle - What happen if p53 gene inactivated - Cancer associated with p53 mutation - Conclusion - References

1. tumor suppressor Gene
Action of pRB and p53
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By
KAUSHAL KUMAR SAHU
Assistant Professor (Ad Hoc)
Department of Biotechnology
Govt. Digvijay Autonomous P. G. College
Raj-Nandgaon ( C. G. )

2. CONTENTS
• Introduction
• History
• Tumor suppressor gene- pRB
- RB gene
- Role of RB in regulation of cell cycle
- Tumor associated with RB gene mutation
• Tumor suppressor gene- p53
- What is p53 gene?
- Function of p53 gene
- How it regulates cell cycle
- What happen if p53 gene inactivated
- Cancer associated with p53 mutation
- Conclusion
- References
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3. INTRODUCTION
Tumor suppressor proteins –
Tumor suppressor gene act as a cell
brakes; they encode proteins that restrain cell growth
and prevent cells from becoming malignant.
Oncogenes –
Encoded proteins that promote the loss of growth
control and the conversion of cell to a malignant
state.
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4. Fig- (a) Mutated tumor suppressor gene (b) Oncogenes
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5. HISTORY
• The existence of such genes originally came to light
from studies in the late 1960s.
• When normal and malignant rodent cells were fused
to one another. Some of the cell hybrids formed
from this type of fusion lost their malignant
characteristics, suggesting that a normal cell
possesses factors that can suppress the
uncontrolled growth of a cancer cell.
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6. Tumor suppressor gene - pRB
• Tumor suppressor protein is a product of tumor
suppressor gene.
• It regulate cell growth by applying brake to cell
proliferation (Growth inhibition).
• Failure to growth inhibition cause carcinogenesis.
• And loss of function of this pRB gene is a key
events in carcinogenesis.
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7. Loss Of Heterozygosity –
• Both normal alleles of normal function of
tumor suppressor gene tumor suppressor
gene.
• One allele active normal function of
(normal) and another tumor suppressor
abnormal (inactive) gene.
(Heterozygous state)
• Both are abnormal loss of function of tumor
(inactive) suppressor gene.
(loss of heterozygosity ) cause mutation
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9. RB gene
• 1st discovered tumor suppressor gene.
• RB stand for Retinoblastoma.
• Retinoblastoma is a human childhood disease,
involving a tumor of retina.
• It occur both as a heritable trait and sporadically.
• It is often associated with deletion of band q14 of
chromosome 13.
• Retinoblastoma arises when both copies of RB gene
are inactivated.
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10. Fig- (a) Sporadic case (b) Inherited case 10

11. Role of RB in regulation of cell
cycle
• The protein encoded by the RB gene, pRB, helps
regulate the passage of cells from the G1 stage of
the cell cycle into S phase.
• From G1 to S is a time of commitment for the cell;
once a cell enters S phase, it invariably proceeds
through the remainder of the cell cycle and into
mitosis.
• The transition from G1 to S is accompanied by the
activation of many different genes that encode
proteins ranging from DNA polymerases to cyclins
and histones.
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12. • Among the transcription factors involved in
activating genes required for S phase activities are
members of the E2F family of transcription factors,
which are key targets of pRB.
• During G1, the unphosphorylated pRB is bound to
the E2F protein.
• The E2F–pRB complex binds to regulatory sites in
the promoter regions involved in cell cycle
progression, acting as a transcriptional repressor
that blocks gene expression.
• At the end of G1 Activation of the cyclin-dependent
kinase (Cdk) leads to the phosphorylation of pRB,
which can no longer bind the E2F protein.
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13. • loss of the bound pRB converts the DNA-bound E2F
into a transcriptional activator, leading to expression
of the genes being regulated.
• The mRNA is translated into protein that are
required for the progression of cells from G1 into S
phase of the cell cycle.
NOTE-
• Some DNA tumor viruses (including adenoviruses,
human papilloma virus, and SV40) encode a protein
that binds to pRB, blocking its ability to bind to E2F.
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14. Fig- Role of pRB in controlling transcription 14

15. Tumor associated with RB gene
mutation
• Retinoblastoma.
• Osteosarcoma.
• Breast cancer.
• Lung cancer.
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16. Tumor suppressor gene - p53
• The most important tumor suppressor is p53 (named
for its molecular size) 53 kDa.
• It is located on band p13 of chromosome 17.
• Also called ‘’Guardian of the Genome’’.
• In 1990,p53 was recognized as the tumor-
suppressor gene.
• Its activity stop formation of tumor.
• Mutation in p53 is the cause of Li-Fraumeni
syndrome, which is rare form of inherited cancer.
• All normal cell have low level of p53.
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17. Function of p53
• DNA repairing.
• Apoptosis.
• Regulation of cell cycle.
• Prevent neoplastic transformation either by
cell cycle arrest or by triggering apoptosis.
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18. DNA damage
Trigger the expression of p53
Increase level of p53
Prevent cell from entering to S phase
It mean arrest of cell cycle at G1 phase
And p53 induce DNA repair gene
DNA repair DNA not repair
Degrade p53 permanent arrest apoptosis
Cell cycle continue
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19. Fig- DNA of cell become damage
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20. How it regulates cell cycle
• Activated p53 encodes a protein called p21 that
inhibits the cyclin-dependent kinase that normally
drives a cell through the G1 checkpoint.
• As the level of p53 rises in the damaged G1 cell,
expression of the p21 gene is activated, and
progression through the cell cycle is arrested.
• This gives the cell time to repair the genetic damage
before it initiates DNA replication.
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21. • Cell cycle arrest is not the only way that p53
protects an organism from developing cancer.
• Alternatively, p53 can direct a genetically damaged
cell along a pathway that leads to death by
apoptosis.
• Including the activation of expression of the BAX
gene, whose encoded product (Bax) initiates
apoptosis.
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22. Fig- p53 activity on damage DNA 22

23. What happen if p53 gene
inactivated
If both copies of the p53 gene are inactivated.
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24. Cancer associated with p53
mutation
• Liver cancer.
• Lung cancer.
• Breast cancer.
• Ovarian cancer.
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25. CONCLUSION
So, pRB and p53 tumor suppressor gene
are very important to inhibit the growth of
tumor or called malignant cancer.
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26. REFERENCES
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