Ras is a family of genes , as well as the proteins that they encode - the so-called small G-proteins (small GTPases ). Ras are membrane-bound proteins involved in signal transduction . They carry out one of the first stages of signal transmission from outside the cell and, as a rule, regulate cell reproduction . Some mutations can lead to continuous activation of Ras, which upsets the regulation of cell division. Errors in the regulation of Ras can lead to tumor growth and metastasis [1] . Indeed, mutations in the Ras gene that increase its activity were detected in 20–25% of human tumors, and in some types of tumors this figure reaches 90% [2] . The superfamily of Ras proteins is a small GTPase and includes Ras, Rho , Arf , Rab G protein and Ran .
History
Ras genes were first identified as transforming oncogenes that caused tumors when infected with Harvey and Kirsten sarcoma virus ( HRAS and KRAS oncogenes, respectively) by Edwin Skolnick et al at National Institutes of Health (NIH), USA . These viruses were first discovered in rats in the 1960s by Jennifer Harvey and Werner Kirsten.
In 1982, Ras activating and transforming human genes were discovered in human cancer cells by Jeffrey Cooper at Harvard , Stuart Aaronson at NIH and Robert Weinberg at MIT . Subsequent studies of neuroblastoma cells led to the discovery of the third RAS gene in humans, called NRAS .
Superfamily
The superfamily Ras includes more than a hundred structurally similar human proteins; the subfamily Ras itself is more than a dozen. In the narrow sense, Ras has four proteins in humans - two forms of protein are read from the KRAS gene due to alternative splicing.
Functions
By participating in signal transduction from membrane receptors, Ras proteins can affect cell proliferation, their attachment to the extracellular matrix , the state of the actin cytoskeleton , malignant transformation, and other processes. Ras are involved in various signal transduction cascades, of which the MAP kinase cascade is the most studied. Malignant transformation of cells can be caused by either Ras point mutations , which cause constant activation of the protein due to impaired ability to hydrolyze GTP, as well as mutations of many proteins involved in the same signal transmission pathway (for example, mutation of the GAP-suppressor gene protein NF1, which promotes the hydrolysis of GTP protein Ras).
Notes
- ↑ Goodsell DS The molecular perspective: the ras oncogene (neopr.) // Oncologist. - 1999. - T. 4 , No. 3 . - S. 263-264 . - PMID 10394594 .
- ↑ Downward J. Targeting RAS signaling pathways in cancer therapy (Eng.) // Nat. Rev. Cancer : journal. - 2003 .-- January ( vol. 3 , no. 1 ). - P. 11-22 . - DOI : 10.1038 / nrc969 . - PMID 12509763 .