Library Core Topics
Foundational Science Series

Core Topics: Cell Biology & Signaling

High-yield reference for cell cycle regulation, apoptosis, signaling pathways, cytoskeleton, and organelles — mapped to USMLE Step 1/2 CK foundational science objectives.

How to Use This Resource

Each topic section includes: Core Concepts (foundational knowledge), Key Regulators/Components (mechanistic details), and High-Yield Facts (exam-focused pearls). Use for active recall, spaced repetition, and integration with clinical cases.

Cell Cycle

Phases, checkpoints, cyclins/CDKs, and tumor suppressor regulation

Cell Cycle Phases
  • G₁ phase: Cell growth, preparation for DNA synthesis
  • S phase: DNA replication (semiconservative)
  • G₂ phase: Preparation for mitosis; protein synthesis
  • M phase: Mitosis (prophase → metaphase → anaphase → telophase) + cytokinesis
  • G₀ phase: Quiescent state; cells exit cycle (neurons, cardiomyocytes)
Checkpoints & Regulators
G₁/S (Restriction Point)
p53, Rb, Cyclin D-CDK4/6
G₂/M Checkpoint
Cyclin B-CDK1; DNA damage arrest
Metaphase Checkpoint
Spindle assembly; prevents anaphase
p21, p27
CDK inhibitors; cell cycle arrest
Tumor Suppressors
  • p53: "Guardian of the genome" → G₁ arrest (via p21) or apoptosis; mutated in >50% of cancers
  • Rb (Retinoblastoma): Binds/inhibits E2F transcription factor; phosphorylation by CDK releases E2F → S-phase entry
  • HPV oncogenes: E6 degrades p53; E7 inactivates Rb → uncontrolled proliferation
  • Meiosis: Reductional division (Meiosis I) → equational division (Meiosis II); produces haploid gametes
High-Yield: Cell Cycle
Cyclin-CDK Progression
Cyclin D-CDK4/6 → G₁; Cyclin E-CDK2 → G₁/S; Cyclin A-CDK2 → S; Cyclin B-CDK1 → G₂/M
Rb-E2F Axis
Unphosphorylated Rb binds E2F → cell cycle arrest; CDK phosphorylation releases E2F → proliferation
p53 Functions
DNA damage → p53 activation → p21 transcription → CDK inhibition → G₁ arrest OR apoptosis if damage irreparable
Clinical Correlation
Li-Fraumeni syndrome (germline p53 mutation) → early-onset cancers; Retinoblastoma (Rb mutation) → childhood eye tumor

Apoptosis

Programmed cell death pathways and regulatory proteins

Apoptotic Pathways
  • Intrinsic (Mitochondrial): Cellular stress → Bax/Bad activation → mitochondrial outer membrane permeabilization → cytochrome c release → apoptosome (Apaf-1 + caspase-9) → caspase cascade
  • Extrinsic (Death Receptor): FasL/Fas or TNF-α/TNFR binding → DISC formation → caspase-8/10 activation → executioner caspases
  • Convergence: Both pathways activate executioner caspases (3, 6, 7) → cellular dismantling
Bcl-2 Family Regulation
Pro-ApoptoticAnti-Apoptotic
Bax, BakBcl-2, Bcl-xL
Bad, Bid, BimMcl-1, Bcl-w
Promote MOMPInhibit MOMP
↑ in DNA damage, stress↑ in follicular lymphoma t(14;18)
Apoptotic Features
  • Morphology: Cell shrinkage, chromatin condensation (pyknosis), nuclear fragmentation (karyorrhexis), membrane blebbing
  • Biochemical: DNA laddering (endonuclease activation), phosphatidylserine externalization (Annexin V binding)
  • Clearance: Apoptotic bodies phagocytosed by macrophages → no inflammation
  • vs Necrosis: Apoptosis = energy-dependent, programmed, non-inflammatory; Necrosis = passive, accidental, inflammatory
High-Yield: Apoptosis
Key Caspases
Initiator: 8 (extrinsic), 9 (intrinsic); Executioner: 3 (main), 6, 7
Follicular Lymphoma
t(14;18) → Bcl-2 overexpression → inhibits apoptosis → B-cell accumulation
Fas-FasL System
Critical for immune privilege (eye, testis); defects → autoimmune lymphoproliferative syndrome (ALPS)
Cytochrome c
Mitochondrial release → binds Apaf-1 → apoptosome → caspase-9 activation → intrinsic pathway

Signaling Pathways

Cell surface receptors, second messengers, and downstream cascades

Receptor Types
GPCRs
Gs (↑cAMP), Gi (↓cAMP), Gq (↑IP₃/DAG)
RTKs
Insulin, EGF, PDGF, VEGF → dimerization → autophosphorylation
JAK-STAT
Cytokine receptors → JAK phosphorylation → STAT dimerization → nuclear transcription
Notch
Cell-cell contact → proteolytic cleavage → NICD → transcription
Major Cascades
  • MAPK/ERK: Ras → Raf → MEK → ERK → proliferation/differentiation; mutated in many cancers
  • PI3K/AKT/mTOR: Growth factors → PI3K → PIP₃ → AKT → mTOR → cell survival, growth, metabolism; PTEN inhibits
  • Wnt/β-catenin: Wnt binding → inhibits β-catenin destruction complex → β-catenin nuclear translocation → transcription; APC mutation in FAP
  • TGF-β: Growth inhibition, fibrosis, EMT; Smad-mediated transcription
  • Hedgehog: Developmental patterning; Patched/Smoothered; mutated in basal cell carcinoma
Second Messengers
  • cAMP: Gs → adenylyl cyclase → PKA activation; degraded by phosphodiesterase
  • cGMP: NO → guanylyl cyclase → PKG; vasodilation, phototransduction
  • Ca²⁺: IP₃ → ER release; calmodulin activation; muscle contraction, exocytosis
  • IP₃/DAG: Gq → PLC → PIP₂ cleavage; IP₃ releases Ca²⁺, DAG activates PKC
High-Yield: Signaling Pathways
Toxin Mechanisms
Cholera toxin: ADP-ribosylates Gs → constitutive activation → ↑cAMP → secretory diarrhea; Pertussis toxin: ADP-ribosylates Gi → inhibition → ↑cAMP
Cancer Targets
HER2/neu (ERBB2): Amplified in breast cancer → trastuzumab target; BCR-ABL: Philadelphia chromosome → constitutive TK → imatinib target
mTOR Inhibitors
Sirolimus, everolimus: Block mTOR → inhibit T-cell activation (immunosuppression) and tumor growth
Wnt Pathway
APC mutation: Familial adenomatous polyposis → constitutive β-catenin → colon cancer

Cytoskeleton

Microfilaments, intermediate filaments, microtubules, and motor proteins

Microfilaments (Actin)

  • 7 nm diameter; ATP-dependent polymerization
  • Cell motility, cytokinesis, muscle contraction
  • Drugs: Phalloidin (stabilizes), Cytochalasin (disrupts)

Intermediate Filaments

  • 10 nm diameter; tissue-specific; NO ATP use
  • Keratin: Epithelial cells
  • Vimentin: Mesenchymal cells
  • Desmin: Muscle; Neurofilaments: Neurons
  • GFAP: Astrocytes (marker for gliomas)

Microtubules

  • 25 nm diameter; tubulin (α/β); GTP-dependent
  • Mitotic spindle, cilia/flagella, intracellular transport
  • Kinesin: Anterograde (cell periphery); Dynein: Retrograde (nucleus)
  • Drugs: Colchicine (depolymerizes), Taxanes (stabilize), Vinca alkaloids (depolymerize)
Motor Proteins & Functions
  • Kinesin: Moves cargo toward microtubule (+) end (cell periphery); anterograde axonal transport
  • Dynein: Moves cargo toward (-) end (nucleus); retrograde transport; ciliary/flagellar beating
  • Myosin: Actin-based motor; muscle contraction (myosin II), vesicle transport (myosin V)
  • Cilia/Flagella structure: 9+2 microtubule arrangement; dynein arms generate bending
  • Kartagener syndrome: Dynein arm defect → immotile cilia → chronic sinusitis, bronchiectasis, situs inversus
Drug Targets
Drug ClassTargetClinical Use
ColchicineMicrotubule polymerizationGout (inhibits neutrophil migration)
Taxanes (paclitaxel)Microtubule stabilizationCancer (blocks mitosis)
Vinca alkaloids (vincristine)Microtubule depolymerizationCancer (blocks mitosis)
CytochalasinsActin polymerizationResearch tool
High-Yield: Cytoskeleton
Intermediate Filament Mnemonic
"Keratin Keeps epithelia; Vimentin Vessels/mesenchyme; Desmin Does muscle; Neurofilaments Neurons; GFAP Glia"
Microtubule Drugs
Taxanes stabilize (freeze mitosis); Vincas/Colchicine destabilize (prevent spindle)
Ciliary Dysfunction
Kartagener syndrome: Immotile cilia → chronic respiratory infections + situs inversus
Energy Use
Microfilaments (ATP), Microtubules (GTP); Intermediate filaments use NO nucleotide triphosphates

Organelles

Structure, function, and clinical correlations of cellular compartments

Nucleus & Mitochondria
Nucleus
DNA storage, transcription, nucleolus (rRNA synthesis); nuclear pores regulate transport
Mitochondria
ATP via oxidative phosphorylation; apoptosis regulation (cytochrome c); maternal inheritance; mutations affect high-energy tissues (muscle, brain)
Endomembrane System
  • Rough ER: Ribosome-bound; protein synthesis, N-linked glycosylation, folding (calnexin/calreticulin)
  • Smooth ER: Lipid synthesis, steroid hormone production, detoxification (CYP450), Ca²⁺ storage; proliferates with chronic alcohol/phenobarbital
  • Golgi apparatus: Protein modification (O-glycosylation, sulfation), sorting, packaging into vesicles; cis → medial → trans face
  • Lysosomes: Acid hydrolases (pH ~5); degradation, autophagy; defects → lysosomal storage diseases
  • Peroxisomes: β-oxidation of VLCFAs, H₂O₂ metabolism (catalase); defects → Zellweger syndrome
Protein Degradation
  • Proteasome: Ubiquitin-mediated degradation of misfolded/damaged proteins; ATP-dependent; 26S complex
  • Ubiquitination: E1 (activating) → E2 (conjugating) → E3 (ligase; substrate-specific) → polyubiquitin chain → proteasomal recognition
  • Autophagy: Lysosome-mediated degradation of organelles/proteins; mTOR inhibits, AMPK activates
  • Clinical: Proteasome inhibitors (bortezomib) for multiple myeloma; autophagy defects in neurodegeneration
High-Yield: Organelles
Lysosomal Storage Diseases
I-cell disease: Golgi fails to phosphorylate mannose → lysosomal enzymes secreted; Tay-Sachs: Hexosaminidase A deficiency → GM2 accumulation; Gaucher: Glucocerebrosidase deficiency → most common LSD
Peroxisomal Disorders
Zellweger syndrome: Peroxisome biogenesis defect → VLCFA accumulation, neuronal migration defects
Mitochondrial Inheritance
Maternal only (sperm mitochondria degraded); heteroplasmy → variable expression; affects muscle/brain (MELAS, LHON)
Smooth ER Induction
Chronic alcohol or phenobarbital → smooth ER proliferation → ↑ drug metabolism → tolerance, drug interactions
Back to Library Next: Biochemistry Pathways

Evidence & Further Reading