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.