All ras proteins are polyisoprenylated but only some are palmitoylated

Two dozen cellular proto-oncogenes have been discovered to date through the study of retroviruses and the use of gene transfer. They form a structurally and functionally heterogeneous group. At least five distinct mechanisms are responsible for their conversion to active oncogenes. Recent work provides experimental strategies by which many of these oncogenes, as well as oncogenes of DNA tumor viruses, may be placed into functional categories. These procedures may lead to definition of a small number of common pathways through which the various oncogenes act to transform cells.

https://science.sciencemag.org/content/sci/222/4625/771.full.pdf

Cellular Oncogenes and Multistep Carcinogenesis

https://www.cell.com/cell/pdf/0092-8674(85)90305-8.pdf

In yeast, RAS proteins are controlling elements of adenylate cyclase

https://www.cell.com/cell/pdf/0092-8674(89)90985-9.pdf

A ras-related gene with transformation suppressor activity

It has been well established that specific alterations in members of the ras gene family, H-ras, K-ras and N-ras, can convert them into active oncogenes. These alterations are either point mutations occurring in either codon 12, 13 or 61 or, alternatively, a 5- to 50-fold amplification of the wild-type gene. Activated ras oncogenes have been found in a significant proportion of all tumors but the incidence varies considerably with the tumor type: it is relatively frequent (20-40%) in colorectal cancer and acute myeloid leukemia, but absent or present only rarely in, for example, breast tumors and stomach cancer. No correlation has been found, yet, between the presence of absence of an activated ras gene and the clinical or biological features of the malignancy. The activation of ras oncogenes is only one step in the multistep process of tumor formation. The presence of mutated ras genes in benign polyps of the colon indicates that activation can be an early event, possibly even the initiating event. However, it can also occur later in the course of carcinogenesis to initiate for instance the transition of a benign polyp of the colon into a malignant carcinoma or to convert a primary melanoma into a metastatic tumor. Apparently, the activation of ras genes is not an obligatory event but when it occurs it can contribute to both early and advanced stages of human carcinogenesis.

The ras gene family and human carcinogenesis

The homologue of the viral Kirsten ras (v-Ki-ras) gene found in the human lung carcinoma cell line, Calu-1, has an intron-exon structure similar to that of the human homologue of the viral Harvey ras (v-Ha-ras) gene. A second, potential fourth coding exon is present in the human Ki-ras gene and similar sequences are found in the Kirsten murine sarcoma virus. Cysteine is encoded at the twelfth amino acid position, suggesting that the Calu-1 Ki-ras gene has undergone a mutational activation at the same position as the human Ha-ras gene of the bladder carcinoma cell line, T24. A comparison of their predicted amino acid sequences suggests that ras proteins have a 'constant' region and a 'variable' region. Here we propose a common modular structure for ras gene products in which the variable region forms a physiologically important combining site.

Daniel Birnbaum

Papers

Structure of the Ki- ras gene of the human lung carcinoma cell line Calu-1