The gag-onc fusion protein is a general term for a

fusion protein Fusion proteins or chimeric (kī-ˈmir-ik) proteins (literally, made of parts from different sources) are proteins created through the joining of two or more genes that originally coded for separate proteins. Translation of this ''fusion gene'' r ...

formed from a

group-specific antigen Group-specific antigen, or gag, is the polyprotein that contains the core structural proteins of an Ortervirus (except ''Caulimoviridae''). It was named as such because scientists used to believe it was antigenic. Now it is known that it makes up ...

('gag') gene and that of an

oncogene An oncogene is a gene that has the potential to cause cancer. In tumor cells, these genes are often mutated, or expressed at high levels.

('onc'), a gene that plays a role in the development of a cancer. The name is also written as Gag-v-Onc, with "v" indicating that the Onc sequence resides in a viral genome. ''Onc'' is a generic placeholder for a given specific oncogene, such as

C-jun Transcription factor Jun is a protein that in humans is encoded by the ''JUN'' gene. c-Jun, in combination with protein c-Fos, forms the AP-1 early response transcription factor. It was first identified as the Fos-binding protein p39 and only lat ...

. (In the case of a fusion with C-jun, the resulting "gag-jun" protein is known alternatively as p65).

Background

Gag genes are part of a general architecture for

retroviruses A retrovirus is a type of virus that inserts a DNA copy of its RNA genome into the DNA of a host cell that it invades, thus changing the genome of that cell. Once inside the host cell's cytoplasm, the virus uses its own reverse transcriptase e ...

, viruses that replicate through

reverse transcription A reverse transcriptase (RT) is an enzyme used to generate complementary DNA (cDNA) from an RNA template, a process termed reverse transcription. Reverse transcriptases are used by viruses such as HIV and hepatitis B to replicate their genomes, ...

, where the gag region of the

genome In the fields of molecular biology and genetics, a genome is all the genetic information of an organism. It consists of nucleotide sequences of DNA (or RNA in RNA viruses). The nuclear genome includes protein-coding genes and non-coding ge ...

encodes proteins that constitute the matrix, capsid and nucleocapsid of the mature virus particles. Like in HIV's replication cycle, these proteins are needed for

viral budding Viral shedding is the expulsion and release of virus progeny following successful reproduction during a host (biology), host cell (biology), cell infection. Once replication has been completed and the host cell is exhausted of all resources in ma ...

from the host cell's plasma membrane, where the fully formed

virion A virus is a submicroscopic infectious agent that replicates only inside the living cells of an organism. Viruses infect all life forms, from animals and plants to microorganisms, including bacteria and archaea. Since Dmitri Ivanovsky's 1 ...

s leave the cell to infect other cells.

gag-v-onc

When a viral gene is introduced into the host cell and is sufficient to induce oncogenesis – the creation of cancerous cells – in the infected cell line, the gene is said to be a "viral transforming gene". When this type of gene is

translated Translation is the communication of the meaning of a source-language text by means of an equivalent target-language text. The English language draws a terminological distinction (which does not exist in every language) between ''transla ...

to a protein, the protein is called a "transforming protein". Note that since the viral oncogenes originated from a host genome, the transformation event is different from transduction, which describes the process of introducing non-native genes to a host organism via a viral infection.

Rous sarcoma virus

The Gag-v-Onc fusion protein from the Rous sarcoma virus illustrates the dual role that the fusion protein plays in the viral and host cellular life cycle. For example, the viral gene Src (as in "sarcoma") is not necessary for viral reproduction, but does affect

virulence Virulence is a pathogen's or microorganism's ability to cause damage to a host. In most, especially in animal systems, virulence refers to the degree of damage caused by a microbe to its host. The pathogenicity of an organism—its ability to ca ...

. Due to evidence of conserved

homology Homology may refer to: Sciences Biology *Homology (biology), any characteristic of biological organisms that is derived from a common ancestor * Sequence homology, biological homology between DNA, RNA, or protein sequences *Homologous chrom ...

between the

v-Src v-Src is a gene found in Rous sarcoma virus (RSV) that encodes a tyrosine kinase that causes a type of cancer in chickens. The src gene is oncogenic as it triggers uncontrolled growth in abnormal host cells. It was the first retroviral oncogene ...

gene and its host (animal) genomes, and its non-essential status for viral reproduction, the v-Src gene is likely to have been acquired from a host genome and altered by subsequent mutations. These subsequent mutations are responsible for the oncogenic capabilities of the virus, as the normal (host) version of the Src gene,

c-Src Proto-oncogene tyrosine-protein kinase Src, also known as proto-oncogene c-Src, or simply c-Src (cellular Src; pronounced "sarc", as it is short for sarcoma), is a non-receptor tyrosine kinase protein that in humans is encoded by the ''SRC'' gene ...

promotes survival,

angiogenesis Angiogenesis is the physiological process through which new blood vessels form from pre-existing vessels, formed in the earlier stage of vasculogenesis. Angiogenesis continues the growth of the vasculature by processes of sprouting and splitting ...

, proliferation and invasion pathways. These native pathways are disrupted in the presence of the mutant Src gene (v-Src) such that

oncogenesis Carcinogenesis, also called oncogenesis or tumorigenesis, is the formation of a cancer, whereby normal cells are transformed into cancer cells. The process is characterized by changes at the cellular, genetic, and epigenetic levels and abnor ...

becomes more likely for the infected host cells, since the v-Src gene is

into a functionally distinct version of its host counterpart.

murine leukemia virus

In the case of the

murine leukemia virus The murine leukemia viruses (MLVs or MuLVs) are retroviruses named for their ability to cause cancer in murine (mouse) hosts. Some MLVs may infect other vertebrates. MLVs include both exogenous and endogenous viruses. Replicating MLVs have a pos ...

es, a species of viruses capable of causing cancer in

murine The Old World rats and mice, part of the subfamily Murinae in the family Muridae, comprise at least 519 species. Members of this subfamily are called murines. In terms of species richness, this subfamily is larger than all mammal families excep ...

s (mice), the viral life cycle can also be responsible for oncogenesis through a Gag-v-Onc fusion protein called "Mo-MuLV(src)", which is a Gag-v-Src protein capable of inducing oncogenesis in living mice.

External links

* * http://www.ijbs.com/v06p0730.htm#headingA7

References