Molecular Biology Tutorials

Tumor Suppressor Gene Rb and its Role in Cell Cycle and Cancer


tumor suppressor gene example

Retinoblastoma Protein (pRb) – A Tumor Suppressor Gene/Protein
(The Importance of pRb in Cell Cycle Regulation and Cancer)

What is Retinoblastoma? What is the cause of Retinoblastoma?

Retinoblastoma or RB is a type of cancer affecting the retina of young individuals. RB occurs in the human population both spontaneously and as a heritable disorder. The genetic reason for the occurrence of RB is associated with a structural aberration of the chromosome. In human, the Rb gene is present on the chromosome 13 at the q-14 region. The loss of this region of due to deletion or mutation causes the retinoblastoma.

The condition of retinoblastoma arises only when both the copies of the Rb gene are lost. In the inherited form of the disease, one parental chromosome carries an alteration in this region. A spontaneous mutation in the retinal cells which results in the inactivation of the other copy of Rb gene can cause the tumor development. Thus, the loss of function of Rb protein due to mutation or deletion is the cause of retinoblastoma.

How Rb acts as a tumor suppressor gene?

A tumor suppressor gene is a gene that prevents the development of cancer. When this gene is mutated and its function is lost forever, there is a very high chance of the cell to enter into a cancerous growth.

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Molecular Biology Tutorials

Extrinsic Pathway of Apoptosis (Apoptosis Molecular Mechanism Part 2)


Receptor Mediated Apoptosis

Extrinsic Pathway of Apoptosis
(The Receptor-Mediated Programmed Cell Death Pathway)

In the extrinsic pathway of apoptosis, the death-inducing signal for the programmed cell death is triggered by an external stimulus. For receiving such an external death-inducing signal, the cell possesses plasma membrane receptors specific to each stimulus and thus the extrinsic signalling of apoptosis is also known as the Receptor Mediated programmed cell death pathway.

The external stimuli for the apoptosis in most of the cases will be a cytokine. The most studied cytokine to induce extrinsic pathway of apoptosis is an extracellular messenger protein called Tumor Necrosis Factor (TNF). TNF is so named because it was first discovered as a protein factor which induces cell death in cancerous cells. The TNF cytokine is produced by the cells of the immune system in response towards the adverse conditions. The adverse conditions that can provoke the immune cells to produce TNF are:

Ø  Exposure to radiation

Ø  Introduction of viral toxins

Ø  Exposure to elevated temperature

Ø  Exposure to other toxic substances

The detailed signaling mechanism of TNF-mediated extrinsic pathway of apoptosis is summarized below:

Ø  TNF first binds to its receptor called TNFR1 (Tumor Necrosis Factor Receptor-1) present on the plasma membrane.

Ø  TNFR1 is a member of death receptor family proteins that turn on the apoptotic cell death process in eukaryotic cells.

Ø  TNFR1 is a trans-membrane receptor with an external ligand binding domain and a cytosolic domain.

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Molecular Biology Tutorials

Intrinsic Pathway of Apoptosis (Apoptosis Molecular Mechanism Part 1)


Mitochondrial Apoptosis Signaling

Intrinsic Pathway of Apoptosis
(The Mitochondria Mediated Programmed Cell Death Pathway)

In the previous post, we have discussed the characteristic features and significance of programmed cell death or apoptosis. As we discussed, the stimuli for the execution of programmed cell death can be of internal or external to the apoptotic cell. Based on the source of stimuli, there are two types of apoptosis signaling pathways operate in the cells. They are (1) Intrinsic pathway (stimuli are internal) and (2) Extrinsic pathway (stimuli are external) of apoptosis. Even though both the intrinsic and extrinsic pathways considerably different, there is always cross-talk between these two pathways. In the present post, we will discuss the details of INTRINSIC PATHWAY of apoptosis signalling.

What is meant by Intrinsic Pathway of Apoptosis?

In the intrinsic pathway of apoptosis, the death-inducing stimuli are originated inside the target cell itself. Mitochondria, the powerhouse of the cell, have a significant role in executing the intrinsic pathway of apoptosis. Thus, the intrinsic pathway of apoptosis is also known as the Mitochondria-mediated death pathway.

What are the stimuli for the intrinsic pathway of apoptosis?

Most commonly observed internal stimuli for the initiation of the intrinsic pathway of apoptosis are:

Ø  Severe genetic damage

Ø  Lack of oxygen (hypoxia)

Ø  Very high concentration of cytosolic Ca2+ ions

Ø  Presence of some viral proteins

Ø  Severe oxidative stress due to the production of free radicals

What are Bcl-2 (B-cell lymphoma-2) family proteins?

The intrinsic pathway of apoptosis is facilitated by the members of Bcl-2 family proteins. The members of the Bcl-2 family proteins are characterized by the presence of one or more BH domains (Bcl-2 Homology Domain). The first identified member of Bcl-2 family proteins is Bcl-2 itself. The Bcl-2 was first identified as a cancer-causing oncogene in some human lymphomas. The gene which codes for the Bcl-2 protein was over-expressed in these cancer cells due to translocation. However, later studies have shown that Bcl-2 is not directly acting as an oncogene. They act as the oncogene by promoting the survival of the cancerous cells that would otherwise die by apoptosis.

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Molecular Biology Tutorials

Apoptosis: The Molecular Mechanism of Programmed Cell Death (Short Notes)


Programmed Cell Death Short Notes

Apoptosis: The Programmed Cell Death

What is Apoptosis? Why apoptosis is known as the ‘Programmed Cell Death’?

The total number of cells in an organ or organism is fundamentally fixed to a specific range in all multicellular organisms. In every multi-cellular organism, the cell number is effectively controlled by two strategies- (a) by regulating cell Division and (b) by regulating cell Death. If cells are no longer needed, they commit suicide (self-destruction) by activating an intracellular death signaling programme. Thus, this death process is known as ‘Programmed Cell Death’. This programmed cell death pathway is called Apoptosis.

The term apoptosis in Greek literally mean ‘falling off’. Just like the old leaves ‘falloff’ from the trees without affecting the life of the plant, the apoptotic cell death will not interfere with the functioning of the organ and organism. The most striking feature of apoptosis is that if a cell undergoes the programmed cell death, the neighboring cells are not at all damaged. Apoptotic death of a cell and its subsequent phagocytosis by a neighboring cell or by a macrophage allow the organic components of the death cell to be effectively recycled.

Learn more: Difference between Apoptosis and Necrosis

The apoptosis is better known as the ‘Programmed Cell Death’. It is a natural well-orchestrated, well sequenced and timely executed chain of events leads to the death of a cell.

What are the characteristics of Apoptotic Cell Death?

An apoptotic cell death is characterized by:

Ø  Shrinkage of the cell

Ø  Shrinkage of the nucleus

Ø  Loss of adhesion to the neighboring cells

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Molecular Biology Tutorials

Different Forms of DNA (A-DNA, B-DNA and Z-DNA) A Comparison Table with PPT


A-DNA, B-DNA and Z-DNA

Different Types of DNA Conformations
(A-DNA, B-DNA and Z-DNA: A Comparison Table)

DNA, the genetic information carrier molecule of the cell, is a long polymer of nucleotides and can adopt different types of structural conformations. The various types of conformations that the DNA can adopt depend on different factors such as:

1.      Hydration level
2.      Salt concentration
3.      DNA sequence
4.      Quantity and direction of super-coiling
5.      Presence of chemically modified bases
6.      Different types of metal ions and its concentrations
7.      Presence of polyamines in solution.

The most common types of structural conformations of DNA are named as:

(1).  A-DNA

(2).  B-DNA

(3).  Z-DNA

Among these three types, the most abundant type of DNA is B-DNA, commonly known as Watson-Crick Model of DNA double helix. The present post describes the structural features of A, B and Z forms of DNA in a comparative manner. We will also discuss the similarities and differences between A-DNA, B-DNA and Z-DNA.

(1). A-DNA

A-DNA is a rare type of structural conformation that a DNA can adopt under dehydrating conditions. A-DNA is a double stranded helical structure almost similar to B-DNA but with a shorter and more compact structural organization. A-DNA was discovered by Rosalind Franklin and the credit for the naming of A-DNA and B-DNA was also accounted to her. Important structural features of A-DNA are given below:

Ø  A-DNA is formed from B-DNA under dehydrating condition.

Ø  A-DNA is much wider and flatter than B-DNA.

Ø  Similar to B-DNA, the A-DNA is also a right handed helix.

Ø  The helix diameter of A-DNA is 26 Å.

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