Introduction Definition History Two hit hypothesis Functions Mutation in tumor suppressor genes What is mutation Inherited mutation of TSGs Acquired mutation of TSGs What is Oncogenes? TSGs and Oncogenes : Brakes and accelerators Stop and go signal Examples of TSGs: RB-The retinoblastoma gene P53 protein TSGs &cell suicide Conclusion References

1. Tumor suppressor
gene
By
KAUSHAL KUMAR SAHU
Assistant Professor (Ad Hoc)
Department of Biotechnology
Govt. Digvijay Autonomous P. G. College
Raj-Nandgaon ( C. G. )

2. SYNOPSIS
 Introduction
 Definition
 History
 Two hit hypothesis
 Functions
 Mutation in tumor suppressor genes
 What is mutation
 Inherited mutation of TSGs
 Acquired mutation of TSGs
 What is Oncogenes?
 TSGs and Oncogenes : Brakes and accelerators
 Stop and go signal
 Examples of TSGs:
 RB-The retinoblastoma gene
 P53 protein
 TSGs &cell suicide
 Conclusion
 References

3. INTRODUCTION
 Tumor suppressor genes play a critical role in
regulating when cells are allowed to divide and
increase in number.
 When DNA damage is detected in a cell, some
tumor suppressor genes can stop the cell from
multiplying until the damage is repaired. Also,
specific tumor suppressor genes can stimulate cells
with damaged DNA to commit "cell suicide".
 When tumor suppressor genes don't function
correctly, the cells with DNA damage continue to
divide and can accumulate further DNA damage that

4. Definition:
 A tumor suppressor gene is a gene that reduces the
probability that a cell in a multicellular organisms will
turn into a tumor cell.
 It is a gene that protects a cell from one step on the
path to cancer. When this gene is mutated to cause
a loss or reduction in its function, the cell can
progress to cancer.

5. History
 The discovery of TSGs came from the studies of a
rare type of human cancer retinoblastoma which
arises from cell in the body that are converted to a
cancerous state by an unusually small no. Of
mutations.
 The genetic basis of retinoblastoma was explained in
1971 by Alfred knudson of the university of texas. He
proposed two hit model to explain the relationships
between mutations and cancer.
 He proposed that the development of retinoblastoma
requires that both copies of RB gene of a retinal cell
be either eliminated or mutated before the cell give

6. Two-hit hypothesis
 TSGs generally follow the “Two-hit hypothesis”.
 The two-hit hypothesis was first proposed by A.G.
Knudson in 1971 for cases of retinoblastoma.
 It implies that both alleles that code for a particular
gene must be affected to cause cancer..
 This is due to fact that if only 1 allele for the gene is
damaged, the 2nd can still produce the correct
protein.

7. Mutations in tumor suppressor
genes
 Tumor suppressor genes are written in a DNA code
that must be transcribed and translated to make the
protein signal.
 Mutations to the DNA code can turn off a tumor
suppressor gene or disrupt the signal.
 By changing the DNA code of a tumor suppressor
gene, the cell can no longer make a tumor
suppressor signal the cell recognizes. By omitting
one letter in the DNA code,the mutated DNA
message makes no sense to the cell. In response,
the cell may not be able to make the tumor

8. What is mutation?
 Mutations are gene defects. They are abnormal
changes in the DNA of a gene. Mutations involve
changes in the arrangement of the bases that make
up a gene. Even a change in just one base among
the thousands of bases that make up a gene can
have a major effect.
 A mutation can affect the cell in many ways. Some
mutations stop a protein from being made at all.
 Some mutations may cause a gene to be turned on,
and make more of the protein than usual. Some
mutations don't have a noticeable effect, but others
may lead to a disease. For example, a certain

9. What is Oncogenes?
 Most oncogenes are mutations of certain normal
genes called proto-oncogenes. Proto-oncogenes are
the "good" genes that normally control what kind of
cell it is and how often it divides.
 When a proto-oncogene mutates (changes) into an
oncogene, it becomes a "bad" gene that can become
permanently turned on or activated when it is not
supposed to be. When this happens, the cell grows
out of control, which can lead to cancer.
 Oncogene are mutated forms of genes that cause
normal cell to grow out of control and become

10. Oncogenes: Brakes and
Accelerators
 A cell continuously receives messages, both from its
own genes and from other cells. Some messages tell
it to grow, and some tell it to stop and rest - like the
accelerator and brake pedals in a car.
 Tumor-suppressor genes act as a cells
brakes;they encode proteins that restrain cell growth
and prevent cells from becoming malignant.
 Oncogenes, act as accelerators of cell proliferation,
 encode proteins that promote the loss of growth
control and the conversion of a cell to a malignant
state .

11. Stop and go signals
 Built into the cell's machinery, are two signals: the
"go" signal to stay in the cell cycle and keep dividing,
and the "stop" signal to stop dividing and exit the
cell cycle. These "stop" and "go" signals work to
maintain the correct balance of healthy, functioning
cells in the body.
 Tumor suppressor genes* code for proteins that
serve as the "stop" signals that tell a cell to leave the
cell cycle and stop dividing.
 Proto-oncogenes* code for the "go" signals that tell
the cell to stay in the cell cycle and continue to

12. 
 If the "stop" or "go" signals do not function properly,
cells can escape from the tight controls that maintain
the correct number of cells in our body. Cells that
accumulate DNA damage (called mutations) may
lose their ability to respond to or make "stop" signals.

13. Examples of TSGs:
 RB - The retinoblastoma gene
 The first tumor-suppressor protein discovered was
the Retinoblastoma protein (pRb) in human
retinoblastoma.
 Retinoblastoma is a cancerous tumor of the retina. It
occurs in two forms:
 Familial retinoblastoma
 Sporadic retinoblastoma


14. Familial retinoblastoma
[Hereditary]
 In the hereditary form
multiple tumors
usually arise
independently,
affecting both eyes.
 Familial
retinoblastoma occurs
when a baby inherits
from one of its
parents a
chromosome (number

15. Sporadic retinoblastoma [ Non-
hereditary]
 A single tumor appears in one eye sometime in early
childhood before the retina is fully developed.
 In these disease both inherited Rb genes are
normal.
 2 somatic mutations are required in a single
retinoblastoma cell for tumor development.
 Thus, sporadic RB arise when both copies of RB are
mutated or lost during development (Knudson’s two
hit hypothesis).

16. Fig: Mutations in the RB gene that
can lead to retinoblastoma
 Sporadic (Non-hereditary) form Familial
[Hereditary] form

17. p53 tumor-suppressor protein
(Guardian of the genome)
 Another important tumor suppressor is the p53
tumor-suppressor protein encoded by the TP53 gene
also known as protein 53 or tumor protein 53.
 p53 was identified in 1979 by Lionel Crawford.
 It is One of the most frequently altered gene in
cancer which monitors DNA damage.
 When DNA in a cell is too damaged, p53 normally
sends a signal that tells the cell to commit suicide.

18. Role of p53
 The cell can monitor itself for DNA damage during
the cell cycle. If DNA damage is detected, the p53
protein plays an important role in putting a "brake"
on the cell cycle.
 The p53 protein prevents a cell from completing the
cell cycle if:-
 Its DNA is damaged or
 The cell has suffered other types of damage.

19.  When :-
 The damage is minor, p53 halts the cell cycle
— hence cell division — until the damage is
repaired.
 The damage is major and cannot be repaired,
p53 triggers the cell to commit suicide by
apoptosis.
 These functions make p53 a key player in
protecting us against cancer; that is, it is an
important tumor suppressor gene.

20. Fig:-A model for the function of
p53.

21. Conclusion
 Tumor suppressor genes function as guardians of
our cells by preventing cells with DNA damage from
dividing and passing on harmful mutations to
daughter cells. Some tumor suppressor proteins
function as a braking signal that stops the cell cycle
when a cell with DNA damage is detected and needs
to be repaired. Other tumor suppressor proteins
instruct a cell with damaged DNA to commit cell
suicide.
 Many researchers are very hopeful about the future
of cancer therapies using oncogenes and tumor

22. References:-
 1. GENE VIII -: BY BENJAMIN LEWIN
 2. CELL AND MOLECULAR BIOLOGY 4TH
EDITION -: BY GERALD KARP
 3. MOLECULAR BIOLOGY OF THE CELL -: BY
ALBERTS
 4. CELL AND MOLECULAR BIOLOGY -: BY
LODISH
 WEBSITES
 www.cancer.org
 www.google.co.in