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Tumor suppressor gene
 
 
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A tumor suppressor gene, or antioncogene is a gene
Gene

A gene is the basic unit of heredity in a living organism. All living things depend on genes. Genes hold the information to build and maintain their cell and pass genetic trait to offspring....
 that protects a cell
Cell (biology)

The cell is the structural and functional unit of all known Life organisms. It is the smallest unit of an organism that is classified as living, and is often called the building bricks of life....
 from one step on the path to cancer. When this gene is mutated to cause a loss or reduction in its function, the cell can progress to cancer, usually in combination with other genetic changes.

ke oncogenes, tumor suppressor genes generally follow the 'two-hit hypothesis', which implies that both alleles that code for a particular gene must be affected before an effect is manifested.






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A tumor suppressor gene, or antioncogene is a gene
Gene

A gene is the basic unit of heredity in a living organism. All living things depend on genes. Genes hold the information to build and maintain their cell and pass genetic trait to offspring....
 that protects a cell
Cell (biology)

The cell is the structural and functional unit of all known Life organisms. It is the smallest unit of an organism that is classified as living, and is often called the building bricks of life....
 from one step on the path to cancer. When this gene is mutated to cause a loss or reduction in its function, the cell can progress to cancer, usually in combination with other genetic changes.

Two-hit hypothesis

Unlike oncogenes, tumor suppressor genes generally follow the 'two-hit hypothesis', which implies that both alleles that code for a particular gene must be affected before an effect is manifested. This is due to the fact that if only one allele for the gene is damaged, the second can still produce the correct protein. In other words, mutant tumor suppressors alleles are usually recessive
Dominance relationship

In genetics, dominance describes the effects of the different versions of a particular gene on the phenotype of an organism. Many animals and plants have diploid in their genome, one inherited from each parent....
 whereas mutant oncogene alleles are typically dominant
Dominance relationship

In genetics, dominance describes the effects of the different versions of a particular gene on the phenotype of an organism. Many animals and plants have diploid in their genome, one inherited from each parent....
. The two hit hypothesis was first proposed by A.G. Knudson for cases of retinoblastoma
Retinoblastoma

Retinoblastoma is a rapidly developing cancer which develops in the cells of the retina, the light sensitive cells of the eye. In the developed world, Rb has one of the best cure rates of all childhood cancers , with more than nine out of every ten sufferers surviving into adulthood....
. Knudson observed that the age of onset of retinoblastoma followed 2nd-order
Degree of a polynomial

When a polynomial is expressed as a sum or difference of term s , the exponent of the term with the highest exponent is the degree of the polynomial....
 kinetics, implying that two independent genetic events were necessary. He recognized that this was consistent with a recessive mutation involving a single gene, but requiring biallelic mutation. Oncogene
Oncogene

An oncogene is a gene that, when mutated or expressed at high levels, helps turn a normal cell into a cancer cell.Many cells normally undergo a programmed form of death ....
 mutations, in contrast, generally involve a single allele because they are gain of function mutations. There are notable exceptions to the 'two hit' rule for tumors suppressors, such as certain mutations in the p53 gene product. p53 mutations can function as a 'dominant negative', meaning that a mutated p53 protein can prevent the function of normal protein from the un-mutated allele. Other tumor suppressor genes which are exceptions to the 'two-hit' rule are those which exhibit haploinsufficiency
Haploinsufficiency

Haploinsufficiency occurs when a diploid organism only has a single functional copy of a wild-type gene and the single functional copy of the gene does not produce enough of a gene product to bring about a wild-type condition, leading to an abnormal or diseased state....
. An example of this is the p27Kip1
P27 (gene)

p27Kip1, is a gene which lies on chromosome 12 in humans and encodes a protein which belongs to the Cip/Kip family of cyclin dependent kinase inhibitor proteins....
 cell cycle inhibitor, in which mutation of a single allele causes increased carcinogen susceptibility.

Functions

Tumor suppressor genes, or more precisely, the protein
Protein

Proteins are organic compounds made of amino acids arranged in a linear chain and joined together by peptide bonds between the carboxyl and amino groups of adjacent amino acid Residue ....
s for which they code, either have a dampening or repressive effect on the regulation of the cell cycle
Cell cycle

The cell cycle, or cell-division cycle, is the series of events that take place in a cell leading to its division and duplication . In cells without a nucleus , the cell cycle occurs via a process termed binary fission....
 or promote apoptosis
Apoptosis

Apoptosis is the process of programmed cell death that may occur in multicellular organisms. Programmed Cell death involves a series of biochemical events leading to a characteristic cell Morphology and death, in more specific terms, a series of biochemical events that lead to a variety of morphological changes, including Bleb , changes...
, and sometimes do both. The functions of tumor suppressor proteins fall into several categories including the following:
  1. Repression of genes that are essential for the continuing of the cell cycle. If these genes are not expressed
    Protein expression

    Protein expression is a subcomponent of gene expression. It consists of the stages after DNA has been translated into amino acid chains, which are ultimately folded into proteins....
    , the cell cycle will not continue, effectively inhibiting cell division
    Cell division

    Cell division is a process by which a cell , called the parent cell, divides into two or more cells, called daughter cells. Cell division is usually a small segment of a larger cell cycle....
    .
  2. Coupling the cell cycle to DNA damage. As long as there is damaged DNA
    DNA

    Deoxyribonucleic acid is a nucleic acid that contains the genetics instructions used in the development and functioning of all known living organisms and some viruses....
     in the cell, it should not divide. If the damage can be repaired, the cell cycle can continue.
  3. If the damage cannot be repaired, the cell should initiate apoptosis
    Apoptosis

    Apoptosis is the process of programmed cell death that may occur in multicellular organisms. Programmed Cell death involves a series of biochemical events leading to a characteristic cell Morphology and death, in more specific terms, a series of biochemical events that lead to a variety of morphological changes, including Bleb , changes...
     (programmed cell death) to remove the threat it poses for the greater good of the organism.
  4. Some proteins involved in cell adhesion
    Cell adhesion

    Cellular adhesion is the binding of a cell to another cell or to a surface or extracellular matrix. Cellular adhesion is regulated by specific cell adhesion molecules that interact with other molecules....
     prevent tumor cells from dispersing, block loss of contact inhibition
    Contact inhibition

    Contact inhibition is the natural process of arresting cell growth when two or more cells come into contact with each other. Oncologists use this property to distinguish between normal and cancerous cells....
    , and inhibit metastasis
    Metastasis

    Metastasis , or Metastatic disease, sometimes abbreviated mets, is the spread of a disease from one Organ or part to another non-adjacent organ or part....
    . These proteins are known as metastasis suppressor
    Metastasis suppressor

    A metastasis suppressor is a protein that acts to slow or prevent metastases from spreading in the body of an organism with cancer. These proteins are different from ones that act to Tumor suppressor gene....
    s.


Examples

The first tumor suppressor protein discovered was the Retinoblastoma protein
Retinoblastoma protein

The retinoblastoma protein is a tumor suppressor protein that is dysfunctional in many types of cancer. One highly studied function of pRb is to prevent excessive cell growth by inhibiting cell cycle progression until a cell is ready to divide....
 (pRb) in human retinoblastoma
Retinoblastoma

Retinoblastoma is a rapidly developing cancer which develops in the cells of the retina, the light sensitive cells of the eye. In the developed world, Rb has one of the best cure rates of all childhood cancers , with more than nine out of every ten sufferers surviving into adulthood....
; however, recent evidence has also implicated pRb as a tumor survival factor.

Another important tumor suppressor is the p53
P53

p53 , is a transcription factor which in humans is encoded by the TP53 gene. p53 is important in multicellular organisms, where it regulates the cell cycle and thus functions as a tumor suppressor that is involved in preventing cancer....
 tumor suppressor protein encoded by the TP53 gene. Homozygous loss of p53 is found in 70% of colon cancers, 30-50% of breast cancers and 50% of lung cancers. Mutated p53 is also involved in the pathophysiology of leukemias, lymphomas, sarcomas and neurogenic tumors. Abnormalities of the p53 gene can be inherited in Li-Fraumeni syndrome
Li-Fraumeni syndrome

Li-Fraumeni syndrome is a rare autosomal dominant hereditary disorder. It is named after Frederick Pei Li and Joseph F. Fraumeni, Jr., the American physicians who first recognized and described the syndrome....
 (LFS), which increases the risk of developing various types of cancers.

PTEN
PTEN

PTEN may mean:* Patterson-UTI Energy, Inc., which trades on the NASDAQ stock market under the symbol 'PTEN'* Prime Time Entertainment Network...
 acts by opposing the action of PI3K, which is essential for anti-apoptotic, pro-tumorogenic Akt
AKT

AKT protein family, which members are also called protein kinases B plays an important role in Mammal cellular signaling....
 activation.

Other examples of tumour suppressors include APC
APC (gene)

APC is a human gene that is classified as a tumor suppressor gene. Tumor suppressor genes prevent the uncontrolled growth of cells that may result in cancerous tumors....
 and CD95.

See also

  • Metastasis suppressor
    Metastasis suppressor

    A metastasis suppressor is a protein that acts to slow or prevent metastases from spreading in the body of an organism with cancer. These proteins are different from ones that act to Tumor suppressor gene....
  • Adenomatosis polyposis coli
    APC (gene)

    APC is a human gene that is classified as a tumor suppressor gene. Tumor suppressor genes prevent the uncontrolled growth of cells that may result in cancerous tumors....
  • Oncogene
    Oncogene

    An oncogene is a gene that, when mutated or expressed at high levels, helps turn a normal cell into a cancer cell.Many cells normally undergo a programmed form of death ....
  • Cancer
    Cancer

    Cancer is a class of diseases in which a group of cell display uncontrolled growth , invasion , and sometimes metastasis . These three malignant properties of cancers differentiate them from benign tumors, which are self-limited, do not invade or metastasize....
  • DNA repair
    DNA repair

    DNA repair refers to a collection of processes by which a cell identifies and corrects damage to the DNA molecules that encode its genome. In human cells, both normal metabolism activities and environmental factors such as UV light and Radiation can cause DNA damage, resulting in as many as 1 million individual molecular lesions per cell pe...
  • Signal transduction
    Signal transduction

    In biology, 'signal transduction' refers to any process by which a cell converts one kind of signal or stimulus into another. Most processes of signal transduction involve ordered sequences of biochemistry chemical reaction inside the cell, which are carried out by enzymes, activated by Second messenger systems, resulting in a signal tran...
  • Von Hippel Lindau Binding protein 1
    Von Hippel Lindau Binding protein 1

    von Hippel-Lindau?binding protein 1 , also known as "prefoldin 3", is a chaperone protein that binds to von Hippel-Lindau tumor suppressor and transports it from perinuclear granules to the Cell nucleus or cytoplasm inside the cell ....


  • p53
    P53

    p53 , is a transcription factor which in humans is encoded by the TP53 gene. p53 is important in multicellular organisms, where it regulates the cell cycle and thus functions as a tumor suppressor that is involved in preventing cancer....


External links

  • , online textbook.
  • , online textbook.
  • , online textbook.