And Rolling!!!. Shh!!! QUIET!!!!. P53 TUMOR SUPPRESSOR. GENE. TABLE OF CONTENTS. DEF. / FUNCTION. WORK CITED. LOCATION. ANATOMY OF P53. LOSS OF FUNCTION CAUSES. PHOTO'S. "GATE KEEPER OF THE GENOME".
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P53 TUMOR SUPPRESSOR
TABLE OF CONTENTS
DEF. / FUNCTION
ANATOMY OF P53
LOSS OF FUNCTION CAUSES
"GATE KEEPER OF THE GENOME"
DEF: A gene which encodes a protein that regulates all growth and is able to cause potential cancerous cells to destroy themselves. The gene is an antioncogen.
F(x): Includes regulation of critical cellular function involving the G1 and G2 cell-cycle check points in response to DNA damage and apoptosis induced by certain stimuli, such as DNA damaging agents and hypoxia.
Additional F(x): The tumor suppressor gene functions as the “guardian of the genome” plays a pivotal roe in “sending” damaged DNA and in making critical decisions of whether a cell should repair the damaged DNA.
Nuclear Protein Genes
P53 Codes for p53 protein which can induce apoptosis
RB Codes for pRB protein, a component of the cell cycle clock
MTS1 Codes for p16 protein, a component of the cell cycle clock
The tumor suppressor gene p53 is located at chromosomes region 17p13 and is one of the most frequently mutated gene in human cancers.
MUTATION:LOSS OF FUNCTION
In humans it is a 393 residue phosphoprotein that is a tumor suppressor gene and is often found mutated in smokers with lung cancer by a compound found in tobacco smoke a polycyclic aromatic hydrocarbon called benzo (a) pyrene. Loss of suppressor genes lead to cancer. Cancer is a state of uncontrolled cell growth. In healthy cells, cell growth is regulated by proto-oncogenes and tumor suppressor proteins. Mutations caused by a variety of factors can stimulate the development of proto-oncogenes into oncogenes and can affect the availability of tumor suppressor proteins
"Mutations in p53 or the pathway that directly regulates it have been found in over 80% of human tumors..."
- Lozano and Elledge (2000)
CIGARETTE TAR ARTICLE
The study, published in Thursday's issue of the journal Science, says the factor is found in the tar of cigarette smoke.
"We have found a specific component of cigarette smoke, benzo pyrene, to be very strongly implicated in lung cancer development," said Gerd Pfeifer, a researcher at City of Hope Medical Center, a cancer center near Los Angeles.
Pfeifer says scientists knew tobacco tar contained numerous possible cancer-causing agents, but now he says his team has pinpointed the exact one. When the scientists put the benzo (a) pyrene chemical compound on human lung cells, a gene called p53 that normally keeps tumors from forming was damaged.
Click here to View the structure of benzo (a) pyrene
Benzo(a)pyrene, a chemical produced by internal combusion engines and thus common in the environment, is not itself mutagenic. However, in the mammalian liver, benzo(a)pyrene is metabolized to diol epoxide, which binds covalently to guanine bases, preventing proper base pairing with cytosine bases. Bulky Addition Products such as diol epoxide or Aflatoxin B1 may result in depurination mutagenesis and are known to be carcinogens.
Another factor that influences p53 mutation is caused by exposure to Ultra Violet Radiation
This schematic ribbon drawing shows three molecules of p53 (red, yellow, purple) interacting with DNA fragments (blue and green). Courtesy of Nikola Pavletich. Reprinted with permission from "Crystal Structure of a p53 Tumor Suppressor-DNA