REGULASI EKSPRESI GEN PADA PROTEIN CASPASE 9 YANG BERPERAN PADA JALUR APOPTOSIS

Summary

This video explores the molecular mechanisms of apoptosis, focusing on caspase-9's pivotal role in regulating programmed cell death. It explains both the extrinsic and intrinsic apoptosis pathways, highlighting how caspase-9 is activated through apoptosome formation and its subsequent activation of other caspases. The transcript also covers the regulation of caspase-9 at the transcriptional, translational, and post-translational levels, including the roles of microRNAs and inhibitory proteins. Understanding these processes is crucial, as dysregulation can lead to diseases such as cancer, where apoptosis is either impaired or occurs abnormally.

Takeaways

• 😀 Apoptosis is a programmed cell death process essential for development, growth, and eliminating damaged cells.
• 😀 Apoptosis is triggered by both extrinsic and intrinsic pathways, each with unique mechanisms for initiating cell death.
• 😀 The extrinsic apoptosis pathway is activated by external signals, such as FasL binding to the Fas receptor on target cells.
• 😀 The intrinsic apoptosis pathway is triggered by internal cellular stress, involving mitochondrial proteins like Bcl-2 and Bax.
• 😀 Caspase 9 plays a key role in the intrinsic apoptosis pathway by activating caspase cascades that execute cell death.
• 😀 Caspase activation leads to cellular destruction, including DNA fragmentation and cell membrane breakdown.
• 😀 The apoptosome complex, formed by cytochrome c, Apaf-1, and ATP, is central to activating caspase 9 during intrinsic apoptosis.
• 😀 The regulation of caspase 9 expression involves transcription factors like p53, which responds to DNA damage and enhances caspase 9 activity.
• 😀 Post-translational regulation of caspase 9 involves inhibitors like XIAP, which can bind to and block its activation.
• 😀 Dysregulation of apoptosis can lead to diseases like cancer, where cells may resist programmed death and continue to proliferate.

Q & A

What is apoptosis, and why is it important?

Apoptosis is a programmed cell death process essential for eliminating damaged or unnecessary cells. It plays a critical role in development, tissue homeostasis, and immune function, including eliminating abnormal or infected cells.

What are the two main pathways involved in apoptosis?

The two main pathways of apoptosis are the extrinsic pathway, initiated by external signals such as Fas ligand binding to the Fas receptor, and the intrinsic pathway, which is triggered by internal stress signals like mitochondrial dysfunction.

How does the extrinsic apoptosis pathway work?

In the extrinsic pathway, the Fas ligand on the surface of immune cells binds to the Fas receptor on target cells. This binding triggers a cascade of intracellular signaling that ultimately activates caspases, leading to the execution of apoptosis.

What is the role of caspase-9 in apoptosis?

Caspase-9 is an initiator caspase in the intrinsic pathway of apoptosis. It is activated when cytochrome c is released from mitochondria into the cytoplasm, forming the apoptosome complex, which in turn activates caspase-9 to initiate apoptosis.

How does the intrinsic pathway of apoptosis differ from the extrinsic pathway?

The intrinsic pathway is regulated by internal signals, primarily related to mitochondrial changes, such as the release of cytochrome c. In contrast, the extrinsic pathway is initiated by external signals, particularly the binding of death ligands to cell surface receptors like Fas.

What is the role of Bcl-2 family proteins in regulating apoptosis?

The Bcl-2 family of proteins controls apoptosis by balancing pro-apoptotic and anti-apoptotic signals. Anti-apoptotic proteins like Bcl-2 and Bcl-xL prevent apoptosis by inhibiting pro-apoptotic proteins like Bax and Bak, which trigger mitochondrial dysfunction.

What happens during the activation of caspase-9 in the apoptosis process?

Caspase-9 activation occurs when it binds to the apoptosome complex, formed by cytochrome c and Apaf-1. This activation leads to the cleavage of effector caspases, such as caspase-3, which then carry out the cell death by degrading cellular components.

What is the role of microRNAs in regulating caspase-9 expression?

MicroRNAs can regulate caspase-9 by binding to its messenger RNA (mRNA), either inhibiting its translation or promoting its degradation, which prevents the inappropriate activation of apoptosis.

How does the regulation of caspase-9 contribute to cancer progression?

In cancer, dysregulated apoptosis often occurs due to the malfunction of caspase-9 regulation. If apoptosis is inhibited (e.g., by mutations in pro-apoptotic proteins), damaged cells may survive and proliferate, leading to cancer development.

Why is the regulation of caspase-9 critical to maintaining cellular homeostasis?

Caspase-9 regulation ensures that apoptosis occurs only when necessary, such as in response to DNA damage or cellular stress. Improper regulation can lead to either excessive cell death (as in degenerative diseases) or uncontrolled cell survival (as in cancer).