Here we discuss about proto oncogene and oncogene.

1. ONCOGENE
Presented by-
Bhabesh Kalita
Department of Biotechnology
Gauhati University

2. Introduction
• Oncogenes are defined as mutated genes
causing the transformation of normal cells
into cancer cells.
• Proto oncogenes are normal genes, which
involved in cell growth, differentiation and
proliferation.
• Proto oncogene, when altered by mutation
becomes an oncogene.
Proto-oncogene Mutation Oncogene
• The resulted protein encoded by oncogene are
known as oncoprotein.

3. Functions of proto-oncogene
They code for proteins that stimulate-
• Cell division
• Prevent cell differentiation and regulate cell
death(apoptosis)

4. Oncogene activation
The change from a normal proto-oncogene to
a cancer-causing oncogene is
called oncogene activation. It is done by two
ways-
A. Activation of oncogene by viruses i.e.
Viral oncogene.
B. By mutation of normal cellular gene.

5. A. Activation of oncogene by virus
• Viruses that causes cancer are most commonly retroviruses.
• Virus oncogene was first defined by Peyton Rous in 1911 in
Rous sarcoma virus(rsv) that transform chicken embryo
fibroblast in culture and induces large sarcomas.
• RSV was carrying a tumorigenic component. In 1976, this
component was identified as the gene, v-src, which originated
from a cellular genome.
• V-src is a viral oncogene derived from the cellular proto-
oncogene c-src, which RSV uses to promote proliferation of its
host cell.
• Normally c-src, a tyrosine kinase, contains two key regulatory
domains at its C-terminus. These two regulatory domains are
absent in the viral version of this gene, leading to constitutive
activation of v-src and its downstream targets .Thus, the RSV is
able to induce cellular transformation because it carries a
mutated gain-of-function version of a cellular gene, which
results in uncontrolled growth.

6. How did RSV acquire the v-src oncogene?
• As a retrovirus, RSV carries genetic information
in the form of RNA. Upon infecting a cell, it
uses its encoded reverse transcriptase enzyme
to make a DNA copy of its RNA.
• The DNA copy is then translocated into the
nucleus of the host cell and is inserted into the
cellular genome . It is thought that for
proliferation to occur, the retroviral DNA must
incorporate itself directly adjacent to the c-
src gene.

7. • Upon transcription of the viral genome, the RNA
polymerase will continue to transcribe the c-src gene. The
viral RNA transcript along with the c-src gene is then
packaged into a viral particle. In other words, RSV steals a
gene from its host.
• However, in order to become oncogenic, the c-src gene
had to acquire alterations, which would confer a gain-of-
function mutation and turn it into the oncogenic v-src.
This likely happened quickly, as the poor proofreading
ability of viral reverse transcriptase and the high
proliferative ability of viruses allow for quick antigenic drift

8. B. Mechanism for activation in normal
cell(conversion of proto-oncogene into oncogene)
In the absence of viral influences, oncogenes are primarily
activated in one of three ways: chromosomal
rearrangements, gene mutations, and gene amplification

9. 1.Chromosomal rearrangements
• Chromosomal rearrangements
(including chromosome
inversion and translocation) occur when
segments of a chromosome are moved and
recombine in a novel location, either within the
same chromosome or to a non-homologous
one. These rearrangments can result in either
the fusion of a proto-oncogene to regulatory
regions that increase its expression, or the
fusion of two genes that now code a novel
protein with oncogenic function.
• One example of a chromosome translocation

10. Burkitt's Lymphoma:
• Burkitt's lymphoma is a solid tumor of B
lymphocytes, Which produce antibodies.
• The genes for making antibodies are located on
chromosomes 14, 2, and 22. These genes are
expressed only in B lymphocytes because only B
cells have the necessary transcription factors for
the promoters and enhancers needed to turn
these antibody genes "on".
• In most of the cases of Burkitt's lymphoma, a reciprocal translocation has
moved the proto-oncogene c-myc from its normal position on
chromosome 8 to a location close to the enhancers of the antibody heavy chain
genes on chromosome 14. In all the other cases, c-myc has been translocated
close to the antibody genes on chromosome 2 or 22.
• c-myc now finds itself in a region of vigorous gene transcription, and it may
simply be the overproduction of the c-myc product (a transcription factor
essential for mitosis of mammalian cells) that turns the lymphocyte cancerous.
Uncontrolled mitosis of this cell results in a clone of cancer cells, Burkitt's
lymphoma.

11. 2.Gene mutation
Point mutations (the alteration of a single
base pair) can be caused by environmental
carcinogens or occur spontaneously, and these
small genetic changes can alter the
conformation of encoded proteins enough to
confer oncogenic activity. One example of this
is seen in the RAS family of oncogenes.

12. RAS oncogene:
• Ras proteins have two states: the inactive form which is bound to
the guanine nucleotide GDP, and the active form which is bound
to GTP (11).
• The active GTP-bound form is normally inactivated relatively
quickly by GTPase-activating proteins (GAPs) which cause the
hydrolysis of GTP to GDP.
• Many Ras mutations interfere with this process, producing a
constitutively active oncoprotein that triggers signaling pathways
for continuous cell growth.

13. • Point mutations at codons 12, 13 or 61 within
the RAS gene are found in many cancers, the
highest incidence being 90% in pancreatic
cancer cases (12).

14. 3. Gene amplification
• Gene amplification occurs when a
portion of the genome is duplicated,
resulting in a higher than normal copy
number of a certain gene.
• This leads to increased expression of the
amplified genes and, if they are involved
in cell proliferation and survival, can
drive transformation of the cell.
• An example is, amplification of c-myc
proto-oncogene leads to excessive
production of myc protein causing
neuroblastoma. Myc gene encodes

15. Types of oncogene
• Oncogenes, whether gained through viral
infection or a gain of function mutation, can
be classified based on the cellular functions
that they are involved in. Some of these
categories include-
o signal transduction modulators
o transcription factors
o apoptosis regulators
o epigenetic reprogramming enzymes

16. Summary
• Oncogene developed from proto-oncogene.
• Oncogene codes for the protein, called as
oncoprotein, leads to uncontrolled growth of
cell, and cause cancer.
• Oncogenes are classified based on the cellular
functions that they are involved in.

17. References
• Molecular biology of Cancer(2nd edition) by F.
Macdonald, C.H.J. Ford, A.G. Casson
• https://www.cancer.gov/about-cancer
• https://en.wikipedia.org/wiki/Oncogene
• http://www.cubocube.com/dashboard.php?a
=340&b=420&c=1