Gag-onc fusion protein

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The gag-onc fusion protein [1] is a general term for a fusion protein formed from a group-specific antigen ('gag') gene and that of an oncogene ('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. [1] Onc is a generic placeholder for a given specific oncogene, such as C-jun. (In the case of a fusion with C-jun, the resulting "gag-jun" protein is known alternatively as p65). [2]

Contents

Background

Gag genes are part of a general architecture for retroviruses, viruses that replicate through reverse transcription, where the gag region of the genome 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 from the host cell's plasma membrane, where the fully formed virions leave the cell to infect other cells. [3]

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". [4] When this type of gene is translated 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. Due to evidence [5] of conserved homology between the v-Src 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. [6] These subsequent mutations are responsible for the oncogenic capabilities of the virus, as the normal (host) version of the Src gene, c-Src promotes survival, angiogenesis, proliferation and invasion pathways. These native pathways are disrupted in the presence of the mutant Src gene (v-Src) such that oncogenesis becomes more likely for the infected host cells, since the v-Src gene is translated into a functionally distinct version of its host counterpart.

murine leukemia virus

In the case of the murine leukemia viruses, a species of viruses capable of causing cancer in murines (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. [7]

See also

Related Research Articles

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<span class="mw-page-title-main">Kaposi's sarcoma-associated herpesvirus</span> Species of virus

Kaposi's sarcoma-associated herpesvirus (KSHV) is the ninth known human herpesvirus; its formal name according to the International Committee on Taxonomy of Viruses (ICTV) is Human gammaherpesvirus 8, or HHV-8 in short. Like other herpesviruses, its informal names are used interchangeably with its formal ICTV name. This virus causes Kaposi's sarcoma, a cancer commonly occurring in AIDS patients, as well as primary effusion lymphoma, HHV-8-associated multicentric Castleman's disease and KSHV inflammatory cytokine syndrome. It is one of seven currently known human cancer viruses, or oncoviruses. Even after so many years of discovery of KSHV/HHV8, there is no known cure for KSHV associated tumorigenesis.

<span class="mw-page-title-main">Oncovirus</span> Viruses that can cause cancer

An oncovirus or oncogenic virus is a virus that can cause cancer. This term originated from studies of acutely transforming retroviruses in the 1950–60s, when the term "oncornaviruses" was used to denote their RNA virus origin. With the letters "RNA" removed, it now refers to any virus with a DNA or RNA genome causing cancer and is synonymous with "tumor virus" or "cancer virus". The vast majority of human and animal viruses do not cause cancer, probably because of longstanding co-evolution between the virus and its host. Oncoviruses have been important not only in epidemiology, but also in investigations of cell cycle control mechanisms such as the retinoblastoma protein.

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<span class="mw-page-title-main">Viral transformation</span>

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Proto-oncogene tyrosine-protein kinase Src, also known as proto-oncogene c-Src, or simply c-Src, is a non-receptor tyrosine kinase protein that in humans is encoded by the SRC gene. It belongs to a family of Src family kinases and is similar to the v-Src gene of Rous sarcoma virus. It includes an SH2 domain, an SH3 domain and a tyrosine kinase domain. Two transcript variants encoding the same protein have been found for this gene.

<span class="mw-page-title-main">FGR (gene)</span> Protein-coding gene in the species Homo sapiens

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<span class="mw-page-title-main">40S ribosomal protein S30</span> Human gene for 40S ribosomal protein S30

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Peter K. Vogt is an American molecular biologist, virologist and geneticist. His research focuses on retroviruses and viral and cellular oncogenes.

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References

  1. 1 2 Lewin, Benjamin (1999). Genes VII . USA: Oxford University Press. ISBN   978-0198792765.
  2. "Oncogene Protein p65(gag-jun) - MeSH - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2017-07-11.
  3. Principles of Virology, 3rd edition, Vol. 1, Molecular Biology, 2009
  4. Flint, S. Jane (December 1, 2008). Principles of Virology, Vol. 2: Pathogenesis and Control (3 ed.). ASM Press. ISBN   978-1-55581-480-9.
  5. Smart JE, Oppermann H, Czernilofsky AP, Purchio AF, Erikson RL, Bishop JM (October 1981). "Characterization of sites for tyrosine phosphorylation in the transforming protein of Rous sarcoma virus (pp60v-src) and its normal cellular homologue (pp60c-src)". Proc. Natl. Acad. Sci. U.S.A. 78 (10): 6013–7. Bibcode:1981PNAS...78.6013S. doi: 10.1073/pnas.78.10.6013 . PMC   348967 . PMID   6273838.
  6. Swanstrom, R.; Parker, R. C.; Varmus, H. E.; Bishop, J. M. (1983). "Transduction of a cellular oncogene: The genesis of Rous sarcoma virus". Proceedings of the National Academy of Sciences of the United States of America. 80 (9): 2519–2523. Bibcode:1983PNAS...80.2519S. doi: 10.1073/pnas.80.9.2519 . PMC   393857 . PMID   6302692.
  7. Feuerman, M. H.; Lee, W. T.; Pattengale, P. K.; Fan, H. (1988). "Comparison of three recombinant murine leukemia viruses carrying the v-src oncogene of avian sarcoma virus: Differences in in vitro transformation and in vivo pathogenicity". Molecular Carcinogenesis. 1 (1): 57–66. doi:10.1002/mc.2940010112. PMID   2855603. S2CID   24552816.