Oncogene as transcription activator

Molecular Biology

VandanaM.S. Pharm.(Biotechnology)NIPER (Hajipur)

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

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.

Product and function of proto-oncogene

Extracellular growth factors

Transmembrane growth factor receptors

Interacellular signal transduction proteins

Interacellular transcription factors

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.

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

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.

Activation mechanism of proto-oncogene