About RRAS / Related RAS Viral (r-ras) Oncogene:
The r-ras oncogene is a proto-oncogene. It encodes for the GTPase enzyme Ras, which is vital in regulating cellular functions and growth. Alfred Pardee first discovered this gene while studying how viral infection can cause cancerous cells to form [Haines et al., 1982]. The discovery of this gene leads to the understanding that when mutated, it causes uncontrolled cell division and other types of cancers.
RRAS Mechanism
Cells process information by a complex system called signal transduction pathways. Signal transduction starts with extracellular signals transmitted through cell surface receptors and intracellular signalling molecules in the membrane (i.e., G-protein) into the cytosol, which then activates protein kinases and inhibits protein phosphatases leading to gene transcription and eventual cellular responses like cytokine release or apoptosis.
Related RAS Viral (r-ras) Oncogene Structure
The protein is made up of four separate peptides, each with a different function.
Each of the four parts is called domains:
●C-terminal domain (CTD) - stores and regulates ATP levels; functions as an ion channel at low pH
●N-terminal domain (NTD) - binds GTPase proteins which regulate other proteins in the cell by controlling their activity under normal conditions.
●RasGEF domain - stimulates Ras to convert from GDP to GTP form when it binds guanosine triphosphate (GTP), also known as GEFs or GDP/GTP Exchange Factors.
●Kelch repeats the regulatory module (KRRM), a stretch of amino acids that interact with regulators of the cell.
The CTD domain is located near the end of the protein and binds to a specific sequence that induces it to fold into its active form.
RRAS Interactions
The protein is involved in interactions with proteins that regulate cell growth. It has been shown to bind and activate the JAK-STAT signal transduction pathway, which leads to transcriptional activation of various genes involved in division and proliferation. This can lead to uncontrolled cellular replication resulting in tumour formation.[13] The Ras protein interacts with other intracellular signalling pathways like phosphoinositide-dependent kinase (PDK) or mitogen-activated protein kinases (MAP).
Related RAS Viral (r-ras) Oncogene Functions
The protein's function is to act as a signal transducer that then transmits signals within cells.
Ras proteins are involved in activation, cell cycle progression, and differentiation signalling pathways. In addition, Ras also regulates intracellular signalling cascades such as MAPK (Mitogen-Activated Protein Kinase), which controls cell proliferation and apoptosis via extracellular signal molecules like cytokines or hormones.