What is oncogene?
A gene that can cause cancerous transformation in animal cells growing in culture and tumour formation in animals themselves. These genes were first discovered in the genomes of RNA viruses that are capable of inducing tumours in vertebrate hosts. Retroviruses gene such as v-src that cause cancer is an oncogene. At least 20 different viral oncogens usually denoted v-onc have been discovered.
Oncogenes may be of DNA v-onc genes and RNA-v-onc genes.
RNA v-oncogenes: RNA v-oncogenes were first discovered by Peyton Rouse in 1911 in fibrosarcoma in chicken and called the virus as Rous Sarcoma Virus (RSV) and was awarded Nobel prize in the year 1966. Later it was shown that RSV is retrovirus whose RNA genome. The genes gag; pol and env are non transforming genes, whereas, v-src is the transforming gene, required for cancer induction. In 1977 Mitchell Bishop and Harold Varmus showed that a gene very closely related to RSV v-src is present in the normal cellular gene is designated as c-src gene. Later on a large number of c-onc genes have been identified by their representation in retroviruses. Some c-onc genes may be found in more than one retroviruses and more than one c-onc genes may be present in different strains of the same retroviruses.
v-onc gene is actually derived from mRNA so that it contains uninterrupted sequence or seqeunce missing at one or both ends, while the corresponding c-onc may be split gene with exons and introns.
In some, v-onc sequence is expressed as a part of a fusion product and their boundaries can be defined by comparing with the corresponding c-onc.
For example: gag-abl, gag-myc, gag-fos etc. while the v-onc of mos, ras, sis and myc genes having no missing region comparing with its c-onc conterparts.
DNA v-onc genes: SV40 DNA viruses also integrate the small part of their genome into the host cell and the cells become transformed because such viral DNA contains one or more oncogenes. Human genital warts are caused by virus.
In culture, DNA tumor viruses are of two types.
(a) Permissive cells: It can be productively infected, virus components are produced, replication and assembly of particles occur and ultimately cell death, lysis and release of virus particles.
(b) Non permissive cells: It is not productively infected but get transformed by becoming the part of the host genome.
Most oncogenes in these viruses are expressed by alternative splicing.
Papillomaviruses have double stranded circular DNA. In a wart or other benign infections these chromosomes are maintained in the basal cells of the epithelium as plasmids, replicate in parallel with the host cells DNA in the course of ordinary cell division cycles. They remain latent and harmless. Rare genetic accidents can cause the integration of a fragment of such a plasmid into a chromosome of the host altering the environment of the viral genes causing unbalanced production of viral replication protein, which interferes the control of cell division, and thus causing cancer induction.
In papillovirus, two viral genes E6 and E7 encode the product that interact with many host cells proteins, particularly to two key tumor suppressor proteins P53 and RB proteins respectively. Thus RB protein is inactivated by binding with E7 while E6 protein binding leads to ubiquitilation of P53 inducing P53 preoteolysis.
A papillomavirus protein designated E5, which contains only 44 amino acids, spans the plasma membrane and forms a dimer or trimer. Each E5 polypeptide can form a stable complex with one endogenous receptor for PDGF, thereby aggregating two or more PDGF receptors within the plane of the plasma membrane. This mimics hormone mediated receptor dimerization and activation, causing sustained receptor activation and leading to cell proliferation.
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