Lecture 11 - Resisting Cell Death Immortality 2024

What is Apoptosis?

Apoptosis is a crucial biological process of programmed cell death that enables organisms to maintain homeostasis by removing damaged, unnecessary, or potentially harmful cells. This process is characterized by specific cellular changes, including cell shrinkage, chromatin condensation, membrane blebbing, and the formation of apoptotic bodies, which are then phagocytosed by adjacent cells.

What are Oncogenes?

Oncogenes are mutated versions of proto-oncogenes that facilitate the uncontrolled growth and proliferation of cells. These alterations often occur due to mutations, amplifications, or chromosomal translocations, leading to abnormal protein expressions that disrupt normal cell cycle regulation, inhibit apoptosis, and contribute to the formation and progression of tumors.

What do Tumor Suppressor Genes do?

Tumor suppressor genes are critical regulators of the cell cycle that function to inhibit cell division, promote apoptosis, and ensure genomic stability. When these genes lose their function—such as through mutations, deletions, or epigenetic modifications—uncontrolled cell division can occur, leading to tumorigenesis. Notable examples include the p53 and Rb genes.

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

The Bcl-2 family consists of a group of proteins that play a pivotal role in regulating apoptosis by controlling mitochondrial membrane permeability. This family includes anti-apoptotic members like Bcl-2 and Bcl-XL, which prevent apoptosis, and pro-apoptotic members such as Bax and Bak, which promote cell death, thus determining the cell's fate in response to stress signals.

What are Caspases?

Caspases are a family of cysteine proteases that are fundamental to the execution of apoptosis. They exist as inactive proenzymes and are activated through specific cleavage events during apoptosis. Caspases orchestrate the cellular demolition involved in apoptosis by cleaving a variety of substrates, leading to characteristic morphological changes such as cell shrinkage and DNA fragmentation.

What triggers the Intrinsic Pathway of Apoptosis?

The intrinsic pathway of apoptosis is triggered by internal cellular stressors, including severe DNA damage, oxidative stress, or mitochondrial dysfunction. These signals lead to mitochondrial membrane permeabilization, the release of pro-apoptotic factors like cytochrome c, and subsequent activation of apoptotic proteins, culminating in programmed cell death.

What initiates the Extrinsic Pathway of Apoptosis?

The extrinsic pathway of apoptosis is initiated by external signals, particularly through the binding of specific death ligands (such as Fas ligand and TNF-alpha) to their corresponding death receptors on the surface of the target cell. This interaction activates a cascade of signaling pathways that ultimately lead to apoptosis.

What is Cytochrome C's role in apoptosis?

Cytochrome c is a critical protein located in the mitochondria that, upon release into the cytosol following mitochondrial stress, interacts with Apaf-1 to form the apoptosome. This complex subsequently activates initiator caspases, which play essential roles in propagating the apoptotic signal and executing programmed cell death.

What is meant by Resistance to Apoptosis in cancer cells?

Resistance to apoptosis is a hallmark of cancer cells, allowing them to evade programmed cell death that typically serves as a protective mechanism against malignancy. This resistance can result from various factors, including overexpression of anti-apoptotic proteins (e.g., Bcl-2) or loss of function of pro-apoptotic proteins, enabling cancer cells to survive in adverse conditions.

What is Targeted Therapy in Cancer?

Targeted therapy in cancer refers to innovative treatment strategies specifically designed to interfere with particular molecular pathways that are integral to cancer cell survival and growth. These therapies often aim at inhibiting proteins involved in apoptosis regulation, such as using BH3 mimetics that counteract anti-apoptotic signals, thereby restoring the ability of cancer cells to undergo programmed cell death.