molecular biology

1. Oncogene as transcription activator
Molecular Biology
Vandana
M.S. Pharm.(Biotechnology)
NIPER (Hajipur)

2. Oncogene
Oncogenes produce proteins that have the capacity to
stimulate growth and proliferation
They are dominant or gain of function mutations
They may lead to genetic instability, prevent a cell from
becoming a apoptosis or promotes metastasis
Protein encoded may function as growth factors or their
receptors ,signal transducers, transcription factors or cell cycle
component

3. Discovery of oncogene
 First discovered through the ability of Rous sarcoma
virus (RSV) to cause cancer in chickens. Src gene cause
cancer.
 Transfection of cells with src or other oncogenes. e.g.,
ras leads to neoplastic transformation.
 These gene codes for a protein that has been associated
with tyrosine kinase activity,that stimulated growth and
proliferation via protein phosphorylation in signal
transduction pathway.
 All oncogenes have been found in normal cell
equivalent genes or proteins and are termed “proto-
oncogenes”.
 proto-oncogenes produces protein products that
normally enhance cell division or inhibit normal cell
death.

4. Product and function of proto-
oncogene
Extracellular growth factors
Transmembrane growth factor receptors
Interacellular signal transduction proteins
Interacellular transcription factors

5. oncoproteins
• Growth factors – rare but an example is sis which
codes for a mutant PDGF (platelet derived growth
factor)
• Sis is present in cancer causing Simian Sarcoma Virus
• Growth factor receptors- Oncogenes encoding cell
surface receptors that transduce growth promoting
signals have been associated with several types of
cancer.
• e.g., erb b is a mutant form of epidermal growth factor
receptor. This receptor functions as a tyrosine protein
kinase (CT of protein) located on the cytoplamic side of
the membrane with the ligand binding region (NT of
protein) facing the cell exterior.

6. Intracellular transducers e.g., ras (a mutant form of an inner cell surface GTPase) ,
whose function activates a number of other regulatory factors including another
oncogene termed raf (a protein kinase) that work in concert to regulate cell
proliferation via the MAP Kinase Pathway which activates transcription factor
proto-oncogene = ras
Oncogene = mutated ras
Always activated
Always stimulating
proliferation

7. Nuclear transcription factor
Proto-oncogene code for the proteins that send a signal to the nucleus to stimulate
cell division.
These signaling proteins act in a series of steps called signal transduction cascade or
pathway.
These cascade includes a membrane receptor for the signal molecule.transcription
factor in the nucleus that activate the genes for cell division.
Myc is a proto-oncogene that codes for a transcription factor . Mutations in Myc
convert it into an oncogene associated with seventy percent of cancers.
RAS is a another oncogene that normally functions as an ‘on off’ switch in the signal
cascade .
Mutation in RAS cause the signaling pathway to remain “on” leading to uncontrolled
cell growth.

9. Activation mechanism of proto-oncogene