BIOL 2112 Chapter Notes - Chapter 386: Intrinsic Activity, P21, Retinoblastoma Protein

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What is a proto-oncogene and what does it encode? Oncogenes are cancer causing
genes in certain types of viruses. Normal versions of cellular genes called proto-
oncogenes code for proteins that stimulate normal cell growth and division. How is a
proto-oncogene converted to an oncogene? An oncogene arises from a genetic change
that leads to an increase either in the amount of the proto-oncogene’s protein product
or in the intrinsic activity of each protein molecule. The genetic changes that convert
proto-oncogenes to oncogenes fall into three main categories: (1) movement of DNA
within the genome, (2) amplification of a proto-oncogene, (3) point mutations in a
control element in the proto-oncogene itself. What is a tumor-suppressor gene? Cells
contain genes whose normal products inhibit cell division. The proteins they encode help
prevent uncontrolled cell growth. How would mutation of a tumor suppressor gene lead
to cancer? Any mutation that decreases the normal activity of a tumor-suppressor
protein may contribute to the onset of cancer, in effect stimulation growth through the
absence of suppression. List the various functions of tumor suppressor proteins. Repair
damaged DNA preventing cell from accumulating cancer-causing mutations; Control the
adhesion of cells to each other or to the extracellular matrix because proper cell
anchorage is crucial in normal tissues and is often absent in cancers; Others are
components of cell signaling pathways that inhibit the cell cycle. Oncoproteins and
mutated tumor suppressors interfere with cell-cycle-stimulating pathways or cell-cycle-
inhibiting pathways, respectively. What is the normal function of the Ras protein? Relays
a signal from a growth factor receptor on the plasma membrane to a cascade of protein
kinases. The cellular response at the end of the pathway is the synthesis of a protein that
stimulates the cell cycle. Normally such a pathway will not operate unless triggered by
the appropriate growth factor. What is the effect on the cell when the Ras protein is
mutated? It can lead to a production of a hyperactive Ras protein that triggers the kinase
cascade even in the absence of growth factor resulting in increased cell division. Would a
Ras mutation be autosomal dominant or recessive? Recessive Describe why the function
of p53 akes this protei the guardian of the genome. Once the gene is activated, the
p53 protein functions as an activator for several other genes. Often it activates a gene
called p21, whose product halts the cell cycle by binding to cyclin dependent kinases
allowing time for the cell to repair the DNA. What is the effect on the cell when p53 is
mutated? If mutations do accumulate and the cell survives through many divisions as is
more likely if the p53 tumor-suppressor gene is defective or missing cancer may ensue.
F. The p21 protein is a tumor suppressor that halts the cell cycle in order to allow for
DNA repair. Would mutation of p21 be autosomal dominant or recessive? Recessive
Transformation is the conversion of a normal cell to a tumor cell. What does the process
of transformation involve? The development of a malignant tumor is paralleled by a
gradual accumulation of mutations that convert proto-oncogenes to oncogenes and
knock out tumor-suppressor genes. A Ras oncogene and a mutated p53 tumor-
suppressor gene are often involved. About half a dozen changes must occur at the DNA
level for a cell to become fully cancerous. These changes usually include the appearance
of at least one active oncogene and the mutation or loss of several tumor-suppressor
genes. What is the usual fate of transformed cells? Apoptosis cellular agents chop up
the DNA and fragment the organelles and other cytoplasmic components. The cell shrinks
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Document Summary

Oncogenes are cancer causing genes in certain types of viruses. Normal versions of cellular genes called proto- oncogenes code for proteins that stimulate normal cell growth and division. An oncogene arises from a genetic change that leads to an increase either in the amount of the proto-oncogene"s protein product or in the intrinsic activity of each protein molecule. The genetic changes that convert proto-oncogenes to oncogenes fall into three main categories: (1) movement of dna within the genome, (2) amplification of a proto-oncogene, (3) point mutations in a control element in the proto-oncogene itself. Cells contain genes whose normal products inhibit cell division. The proteins they encode help prevent uncontrolled cell growth. Any mutation that decreases the normal activity of a tumor-suppressor protein may contribute to the onset of cancer, in effect stimulation growth through the absence of suppression. List the various functions of tumor suppressor proteins.

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