Cell Cycle Regulation and Apoptosis

Vocabulary practice flashcards covering cell cycle death mechanisms, apoptosis vs. necrosis, intrinsic and extrinsic signaling cascades, caspase activation, and regulatory proteins from Hakan Ozdener's lecture.

Apoptosis

A controlled, genetically regulated form of programmed cell death characterized by cellular condensation, intact plasma membranes, ATP consumption, and non-inflammatory clearance by phagocytes.

Necrosis

An accidental form of cell death caused by external damage (such as injury or infection), marked by cell swelling, ruptured membranes, ATP depletion, cellular lysis, and the release of intracellular contents that provokes inflammation.

Embryonic Digit Formation

A developmental process occurring during the fifth week of human embryogenesis in which paddle-like hand and foot plates develop ridges, and apoptosis destroys the interdigital tissue to separate individual fingers and toes.

Physiological Apoptotic Clearance Rates

The daily cellular turnover rates via apoptosis: an average child (aged 8 to 14) loses 20 to 30 billion cells per day, whereas an average adult loses 50 to 70 billion cells per day.

Steroid Immunosuppressants

Pharmacological therapeutic agents that diminish immune activity by directly triggering apoptosis in target lymphocytes.

Synaptosis vs. Apoptosis

Two distinct levels of neuronal decline: synaptosis represents the potentially reversible loss of synaptic connections, whereas neuronal apoptosis constitutes irreversible death and loss of the neuronal cell body.

Tissue Atrophy vs. Hyperplasia

The pathological consequences of disrupted apoptotic balance: excessive apoptosis leads to tissue atrophy (e.g., neurodegeneration, thin skin), whereas deficient apoptosis causes hyperplasia and neoplastic survival.

Mitogens

Extracellular signal molecules that stimulate cell division primarily by relieving intracellular negative controls that otherwise block cell cycle progression.

Growth Factors

Extracellular signal molecules that stimulate cell growth (increase in cell mass) by promoting macromolecule and protein synthesis while inhibiting their degradation.

Survival Factors

Extracellular signal molecules that actively promote cell survival through the continuous suppression of apoptotic signaling pathways.

Caspases

A conserved family of at least 12 cysteine-aspartic-acid-proteases synthesized as inactive procaspases that, upon proteolytic cleavage, execute cell disassembly in apoptosis or mediate inflammatory signaling.

Procaspase Activation and Cascade

The proteolytic mechanism where an inactive procaspase is cleaved at specific sites to discard its prodomain and assemble large and small catalytic subunits; an active initiator caspase cleaves and activates multiple executioner caspases, which degrade vital structural proteins such as actin and nuclear lamins.

Extrinsic Pathway

The apoptotic pathway triggered by extracellular death ligands (e.g., FasL, TNF, TRAIL) binding to cell-surface death receptors (e.g., Fas/CD95, TNF-R, DR4/DR5), assembling the DISC complex and activating initiator Caspase-8.

DISC (Death-Inducing Signaling Complex)

A multi-protein signaling complex formed at the intracellular death domains of activated transmembrane death receptors that recruits cytosolic adaptor proteins and procaspase-8 to initiate the extrinsic apoptotic cascade.

Intrinsic (Mitochondrial) Pathway

The apoptotic pathway initiated by internal stresses (such as DNA damage, oxidative stress, or growth factor withdrawal) that cause mitochondrial outer membrane permeabilization (MOMP) and the cytosolic release of cytochrome c.

Cytochrome c

An electron transport chain component normally sequestered within the mitochondrial intermembrane space that, upon stress-induced membrane permeabilization, leaks into the cytosol to assemble the apoptosome.

Apoptosome

A cytosolic multiprotein complex formed by released cytochrome c, Apaf-1, and dATP/ATP that binds and proteolytically activates initiator procaspase-9.

SMAC / DIABLO

Second mitochondrial-derived activator of caspases; a pro-apoptotic protein released from mitochondria into the cytosol that binds to and neutralizes inhibitor of apoptosis proteins (IAPs).

IAPs (Inhibitor of Apoptosis Proteins)

Endogenous regulatory proteins (such as XIAP) that normally suppress apoptosis by directly binding and inactivating caspases.

Bax and Bak

Multi-domain pro-apoptotic effector proteins of the Bcl-2 family that oligomerize in the mitochondrial outer membrane to induce MOMP and release apoptogenic proteins into the cytosol.

BH3-Only Activators

Pro-apoptotic Bcl-2 family members (e.g., BIM, PUMA, tBID) that sense cellular stress and directly activate effector proteins Bax and Bak to initiate mitochondrial permeabilization.

Anti-apoptotic Bcl-2 Proteins

Protective multi-domain proteins (e.g., Bcl-2, Bcl-xL) containing BH1–4 domains that sequester pro-apoptotic BH3-only proteins and effectors to prevent MOMP and prevent apoptosis.

p53 Tumor Suppressor

A master regulatory protein activated by DNA damage that promotes cell cycle arrest, senescence, DNA repair, or apoptosis via transcriptional upregulation of pro-apoptotic BH3-only proteins such as PUMA and NOXA.

MDM2 Inhibition and p53 Degradation

A regulatory mechanism in tumor cells where MDM2 binds wild-type p53 to target it for degradation; targeted by antagonist molecules like BI 907828 to liberate p53, induce nuclear translocation, and trigger apoptotic gene transcription.

Apoptotic Blebbing

A morphological hallmark of apoptosis where the cell shrinks and projects membrane protrusions (blebs) as the cytoskeleton and nuclear lamins are cleaved, culminating in the formation of membrane-enclosed apoptotic bodies.