User:Jeremy Chieh-Yu Chung/Sandbox 1
From Proteopedia
Contents |
RAS PROTEIN
INTRODUCTION
Human beings fear when they hear the term “cancer.” When a person is diagnosed as having cancer, such news is always devastating. So, what is cancer? It is a disease in which cells exhibit uncontrolled growth and invasion that intrudes and kills adjacent tissue, and for most cases, it is lethal. Documents regarding to cancer can date as far back as 460BC, and reports on patients having symptoms resembling that of cancer could be found throughout the history of mankind. Ancient Greek physician Hippocrates described multiple kinds of cancers and referred them as carcinos. Since its discovery approximately 2500 years ago, there still is not a definite cure for the deadly disease. However, throughout the past few decades, with improved technology, medical communities now have a better understanding in treating the disease, or perhaps, slowing the spread of malignant cells. We now know that the onset of cancer is tightly related to the mutation in ras gene. Being involved in 30% of human cancer, hyperactive Ras is currently being heavily investigated as a possible target for novel drugs. Rat Sarcoma protein, also known as Ras, is the functional product of ras gene. It belongs to the large super-family of proteins known as “low-molecular weight G-proteins.” They are referred to as G-proteins due to their abilities to bind to guanine nucleotides (GTP and GDP). Ras is most commonly known by its ability to conduct extracellular signal to inside the cell. Ras triggers and causes responses in more than 20 effectors and regulate processes such as proliferation, survival and differentiation in cells.
HISTORY
RAS protein was first identified to be responsible for cancer causing activities. It was first found in rats, hence the name Rat sarcoma. It was once thought to act only at plasma membrane, but later research showed that it has signal transduction ability.
STRUCTURE
RAS protein is a monomeric globular protein with 189 amino acid residues. Its secondary structure consists six stranded beta sheet and five alpha helices. The G domain of the protein binds to guanosine nucleotides, and it has five motifs that bind to either GTP or GDP. The C terminal is the membrane targeting region.
FUNCTION
The binary switches, which is controlled by an exchange factor, govern intracellular signal transduction. When bound to GDP, RAS is in the inactive state. RAS is in the active state when GTP is bound. RAS protein is crucial in proliferation, adhesion and apoptosis.
ACTIVATION
The activation of Ras signaling leads to cellular differentiation, growth and survival. Its receptor is located in the cell membrane, and its action is regulated by exchange factors and GAP, which catalyzes the hydrolysis of GTP.
MUTATION
RAS protein, when mutated, results in permanent activation of Ras signaling even in the absence of extracellular signals/ growth factors
