Proteins known as cyclins (named because their concentration increases and decre
ID: 15575 • Letter: P
Question
Proteins known as cyclins (named because their concentration increases and decreases in a regular pattern through the cell cycle) and enzymes known as cyclin-dependent kinases (Cdks) are the key components in the regulatory events that occur at checkpoints. At the G1 to S checkpoint, two different G1 cyclin/Cdk complexes form, resulting in activation of the kinases. The kinases catalyze a series of phosphorylations (addition of phosphate groups) of cell-cycle control proteins, affecting the functions of those proteins and leading to transition into the S phase.A similar process occurs at the G2 to M checkpoint. A G2 cyclin binds to a Cdk to form a complex. Until the cell is ready to enter mitosis, phosphorylation of the CdK by another kinase keeps the Cdk inactive. At that time, a phosphatase removes the key phosphate from the Cdk, activating the enzyme. Phosphorylations of proteins by the Cdk move the cell into mitosis.
a. Why are genes encoding cyclins considered proto-oncogenes?
b. Why are mutations in cyclin genes (and in other proto-oncogenes) considered dominant mutations?
Explanation / Answer
Cyclins are proteins that regulate the cell cycle, together with cyclin-dependent kinases. Because cancer always involves cell cycle disturbances, such as uncontrolled cell division with failure to halt in response to DNA damage, mutations in the genes that code for cyclins have definite cancer-causing potential. Cyclin D1, for example, regulates when the cell moves from the G1 (first growth) phase to S (DNA synthesis) phase, and the gene for cyclin D1 is often found to be mutated in certain types of cancer. A proto-oncogene is a normal gene that can cause cancer if the gene becomes mutated or if regulation of its expression goes awry. Genes classified as proto-oncogenes are found in all cells, and they usually play roles in the cell cycle and in cell growth and differentiation. Mutations and overexpression of proto-oncogenes can lead to tumor growth and metastasis. hence it is genes encoding cyclins considered proto-oncogenes Proto-oncogenes are a group of genes that cause normal cells to become cancerous when they are mutatied. Mutations in proto-oncogenes are typically dominant in nature, and the mutated version of a proto-oncogene is called an oncogene. Often, proto-oncogenes encode proteins that function to stimulate cell division, inhibit cell differentiation, and halt cell death. All of these processes are important for normal human development and for the maintenance of tissues and organs. Oncogenes, however, typically exhibit increased production of these proteins, thus leading to increased cell division, decreased cell differentiation, and inhibition of cell death; taken together, these phenotypes define cancer cells. Thus, oncogenes are currently a major molecular target for anti-cancer drug design.
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