7. Proto-oncogenes and Oncogenes

Summary

This video for medical students delves into the molecular basis of cancer, focusing on proto-oncogenes and oncogenes. It explains how mutations in DNA can lead to faulty proteins and cancer's hallmarks. Proto-oncogenes are genes that encourage cell division, and when mutated into oncogenes, they promote uncontrolled cell growth. The video uses the car analogy, comparing tumor suppressor genes to brakes and oncogenes to an accelerator, highlighting the difference between loss of function in tumor suppressors and gain of function in oncogenes, which only requires one mutation to lead to cancer.

Takeaways

• 🧬 Cancer development is linked to DNA mutations that result in faulty proteins and the hallmarks of cancer.
• 🔑 Proto-oncogenes are genes that normally encourage cell division; when mutated, they become oncogenes.
• 🛑 Tumor suppressor genes act as 'brakes' to control cell cycle progression, while oncogenes act as 'accelerators'.
• 🌱 A gain in function of proto-oncogenes, turning them into oncogenes, leads to uncontrolled cell division and cancer growth.
• 🔄 The RAS gene is the most commonly mutated oncogene in human cancers, playing a critical role in cell cycle regulation.
• ⚙️ In normal cells, the RAS protein is inactive when bound to GDP and becomes active upon binding to GTP, a process facilitated by a GTP exchange factor.
• 🔄 The RAS protein activates transcription factors that promote cell cycle progression and division.
• 🛑 The GTPase activity, which involves a GTPase-activating protein (GAP), is crucial for inactivating RAS and controlling cell growth.
• 🧬 Mutations in the RAS protein's GTPase activity can lead to permanent activation and uncontrolled cell division.
• 🔄 For oncogenes, a single mutation can lead to cancer growth due to the gain of function, unlike tumor suppressor genes which require two 'hits'.

Q & A

What are the two main groups of genes involved in cancer development?

The two main groups of genes involved in cancer development are tumor suppressor genes and proto-oncogenes.

How do proto-oncogenes contribute to cell growth and division?

Proto-oncogenes produce proteins that encourage the cell to move through the cell cycle and divide. When they mutate, they become oncogenes that promote cell division and the development of cancer.

What is the difference between proto-oncogenes and oncogenes?

Proto-oncogenes are the normal forms of genes that encourage cell division. Oncogenes are mutated forms of proto-oncogenes that are active all the time, promoting uncontrolled cell division.

How do oncogenes differ from tumor suppressor genes in terms of function?

Tumor suppressor genes act like brakes to stop cells from moving through the cell cycle, while oncogenes act like accelerators, promoting cell growth and division.

Why is a gain of function in proto-oncogenes significant for cancer development?

A gain of function in proto-oncogenes turns them into oncogenes, which can lead to uncontrolled cell division and cancer development because only one copy of the gene needs to mutate for this to occur.

What is the role of the RAS protein in normal cell function?

In normal cells, the RAS protein is bound to GDP and must be activated by exchanging GDP for GTP, which is facilitated by a GTP exchange factor. This activation leads to the progression of the cell cycle and cell division.

How does the RAS protein become active, and what is its role in cell division?

The RAS protein becomes active by substituting GDP for GTP, which is facilitated by a GTP exchange factor. Once active, it activates transcription factors that lead to the activation of genes involved in cell cycle progression and division.

What is the significance of the GTPase activity in the RAS protein?

GTPase activity is significant because it deactivates the RAS protein by breaking down GTP to GDP, providing a way to control the RAS activity and thus controlling cell growth and division.

What happens if the GTPase activity portion of the RAS protein mutates?

If the GTPase activity portion of the RAS protein mutates, it may not be able to break down GTP, leading to the RAS protein being permanently active and causing uncontrolled cell division.

How does the mutation of proto-oncogenes differ from that of tumor suppressor genes in terms of cancer development?

For tumor suppressor genes, both copies need to be inactivated (two hits) to lead to cancer development, whereas for oncogenes, only one mutation is needed to promote cancer growth due to a gain of function.

Outlines

00:00

🧬 Understanding Proto-oncogenes and Oncogenes

This paragraph delves into the molecular basis of cancer, focusing on proto-oncogenes and oncogenes. It explains how mutations in DNA can lead to the production of faulty proteins, which in turn give cells cancerous characteristics known as the 'hallmarks of cancer.' Proto-oncogenes are genes that, in their normal state, encourage cell division. However, when mutated, they become oncogenes, promoting uncontrolled cell division and cancer development. The video uses the analogy of a car's accelerator to describe oncogenes, emphasizing that only one mutation is needed to activate the oncogene and lead to cancer. The Ras gene and its role in cell cycle regulation are also discussed, highlighting how mutations in the gene's GTPase activity can result in permanent activation and uncontrolled cell division.

05:03

🛑 The Impact of Mutations on Tumor Suppressor Genes and Oncogenes

The second paragraph contrasts the effects of mutations on tumor suppressor genes and oncogenes. It explains that tumor suppressor genes act as 'brakes' on cell division, and both copies must be inactivated (a 'two-hit' scenario) for cancer to develop. In contrast, oncogenes act like an 'accelerator,' and only one mutation is required to promote cancer growth. This distinction is crucial for understanding how genetic mutations can lead to different outcomes in cancer development.

Keywords

💡Proto-oncogenes

Proto-oncogenes are normal genes that encode for proteins which regulate the cell cycle and promote cell growth and division. In the video, it is explained that when these genes mutate in a way that they become active all the time, they can lead to uncontrolled cell division and cancer. Proto-oncogenes are compared to the accelerator pedal in a car, as they promote cell growth and division, which is a key theme of the video.

💡Oncogenes

Oncogenes are mutated forms of proto-oncogenes that contribute to the development of cancer by promoting cell division. The video describes how oncogenes are like the accelerator of a car, constantly pushing the cell to divide, leading to uncontrolled growth. An example given is the mutated form of the RAS gene, which, when it cannot deactivate, leads to continuous cell division.

💡Mutations

Mutations refer to changes in the DNA sequence that can lead to the production of faulty proteins. The video emphasizes that mutations in proto-oncogenes can result in oncogenes, which are a driving force behind cancer development. Mutations are central to understanding the molecular basis of cancer, as they alter the normal function of genes.

💡Cell Cycle

The cell cycle is the series of events that take place in a cell, leading to its division and duplication. In the context of the video, the cell cycle is a critical process that proto-oncogenes and oncogenes influence. Uncontrolled progression through the cell cycle due to mutations in these genes can result in cancer.

💡Tumor Suppressor Genes

Tumor suppressor genes are genes that normally function to prevent cell division and growth when they are not supposed to occur. The video contrasts these with proto-oncogenes and oncogenes, explaining that while tumor suppressor genes act as 'brakes' to cell division, oncogenes act as 'accelerators'. The loss of function in tumor suppressor genes can also contribute to cancer development.

💡Hallmarks of Cancer

The hallmarks of cancer refer to a set of characteristics that cancer cells possess, such as sustained proliferative signaling, evasion of growth suppressors, and resistance to cell death. The video mentions these characteristics as results of mutations leading to faulty proteins, which is a key concept in understanding how cancer cells behave differently from normal cells.

💡GTP (Guanosine Triphosphate)

GTP is a molecule that, when bound to the RAS protein, activates it, leading to cell division. The video explains the process by which GTP replaces GDP on the RAS protein, activating it and initiating a series of events that promote cell cycle progression. This is a crucial step in the normal functioning of proto-oncogenes and a point of failure in oncogenes.

💡GDP (Guanosine Diphosphate)

GDP is a molecule that, when bound to the RAS protein, keeps it in an inactive state. The video describes how the exchange of GDP for GTP is necessary for the activation of the RAS protein, which is a normal part of cell cycle regulation. Mutations that prevent this exchange can lead to uncontrolled cell division.

💡GTPase Activity

GTPase activity refers to the ability of a protein to break down GTP into GDP. In the video, it is explained that the RAS protein must have its GTPase activity to deactivate after it has activated cell division signals. Mutations that impair this activity can lead to permanent activation of the RAS protein and cancer.

💡GTPase-Activating Protein (GAP)

GAPs are proteins that enhance the GTPase activity of other proteins, such as the RAS protein. The video mentions that GAPs help in the inactivation of RAS by promoting the conversion of GTP back to GDP, which is essential for controlling cell division. Mutations affecting GAP function can contribute to uncontrolled cell growth.

💡Gain of Function

Gain of function refers to a mutation that results in a new or enhanced function of a gene or protein. The video explains that in the case of proto-oncogenes turning into oncogenes, a gain of function mutation leads to continuous cell division signals, promoting cancer growth. This concept is central to understanding how oncogenes contribute to cancer.

Highlights

Cancer develops due to mutations in DNA that lead to the production of faulty proteins.

These proteins give cells certain characteristics known as the hallmarks of cancer.

Genes involved in cancer can be divided into tumor suppressor genes and proto-oncogenes.

Proto-oncogenes produce proteins that encourage cell division and movement through the cell cycle.

When proto-oncogenes mutate, they become oncogenes and promote cell division, leading to cancer.

Tumor suppressor genes act as brakes, while oncogenes act as accelerators in cell cycle control.

A gain in function of proto-oncogenes turning them into oncogenes leads to cancer growth.

For a gene to produce a properly functional protein, both copies must be taken out in the case of tumor suppressor genes.

Only one copy of an oncogene needs to mutate to promote cancer growth due to a gain in function.

The most commonly mutated oncogene in human cancers is the RAS gene.

The RAS protein is bound to GDP in its inactive state.

GTP exchange factors activate the RAS protein by substituting GDP with GTP.

Activated RAS protein leads to the activation of genes involved in cell cycle progression and division.

GTPase activity, with the help of GAP proteins, inactivates RAS by breaking down GTP to GDP.

Mutations in the GTPase activity portion of RAS can lead to permanent activation and uncontrolled cell division.

Tumor suppressor genes prevent cell growth and division, while oncogenes promote it.

Loss of function in tumor suppressor genes leads to cancer development, while a gain of function in oncogenes does.

Tumor suppressor genes require two hits (mutations in both copies), whereas oncogenes need only one mutation.

Transcripts

hello and welcome back to oncology for

medical students in this section of

videos on the molecular basis of cancer

this video will cover proto-oncogenes

and oncogenes in

the previous videos we talked about how

cancers develop as a result of mutations

to DNA how these changes lead to the

production of faulty proteins and how

these proteins give the cells certain

characteristics known as the hallmarks

of cancer we've also talked about how

the genes involved in these changes can

also be divided into two groups tumor

suppressor genes covered in the last

video and proto-oncogenes

cells contain many genes that produce

proteins that encourage the cell to move

through the cell cycle and divide the

normal forms of these genes are called

pro so oncogenes when they mutate way

that they are active all the time they

promote cell division on the development

of cancer the mutated forms of these

genes are called oncogenes

where tumor suppressor genes stop the

cells moving through the cell cycle like

the brakes of a car oncogenes are like

the accelerator pedal

where a loss of function of tumor

suppressor genes promote the growth of

cancer it's a gain in function of proton

code genes turning them into oncogenes

that Leeson leads to the growth of

cancers

because we have two copies of each gene

to stop a gene from producing a properly

functional protein both copies have to

be taken out this type of loss of

function applies to tumor suppressor

genes but this isn't the case with

oncogenes because we're talking about

genes that gainer function it's only

necessary for one copy to become mutated

to promote the growth of cancer

the most commonly mutated oncogene in

human cancers is the rats on coaching to

see how it functions again we'll have to

have a look inside the cell

in normal cells in its inactive state

the Rass protein is bound to a molecule

called gdp guanosine diphosphate in

order to become active the Rass gene

must substitute the gdp molecule for

another GTP guanosine triphosphate this

happens by the action of a protein

called a guanosine triphosphate or GTP

exchange factor this type of protein

exchanges the gdp on the inactive rass

protein for a gtp

which activates the wrasse protein

Russ then in turn activates a number of

transcription factors that lead to the

activation of genes involved in

progressing through the cell cycle and

dividing

you

the wrasse protein then deactivates by

the action of something called gtp A's

activity this means it breaks down the

gtp to GDP it does this with the help of

a protein called a GTP A's accelerating

protein or gap

the inactivation is very important it

provides a way of controlling the rats

activity and therefore controlling self

growth and division

if the portion of the wrasse protein

responsible for the gtp A's activity

mutates it may not be able to break down

the gtp this means that the gtp is stuck

bound to the wrasse protein and it's

permanently active leading to

uncontrolled cell division

because the mutation is leading to a

gain of function only one copy of the

gene needs to mutate to causes to happen

now that will cover both tumor

suppressor genes and oncogenes I thought

would finish with a quick comparison

where tumor suppressor genes are

involved in preventing cell growth and

division proto-oncogenes or the mutated

counterparts oncogenes promote cell

growth and division

it's normally a loss of function of

tumor suppressor genes that leads to the

development of cancers whereas on the

other hand with uncle genes it's a gain

of function

to use the car analogy the tumor

suppressor genes are like the car breaks

on the cell cycle and the onion the case

of oncogenes they like the car

accelerator

because we have two copies of each gene

and the case of tumor suppressor genes

you need both copies to be taken out to

lead to the development of cancer so

they need two hits and the case of

oncogenes they just need one mutation

thank you