Cell Cycle and Nuclear Receptors Quiz
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Questions and Answers

Which cyclin is primarily involved in the G1 to S phase transition?

  • Cyclin A/CDK 2
  • Cyclin D/CDK 4,6
  • Cyclin E/CDK 2 (correct)
  • Cyclin B/CDK 1

    • What is the role of the ubiquitin ligase in the degradation of cyclins?

  • It adds a polyubiquitin chain to the cyclin. (correct)
  • It recycles the cyclin back to the cell.
  • It thread the cyclin into the proteasome.
  • It separates cyclin from CDK.

    • Which cyclin is predominantly present during the M phase?

  • Cyclin A/CDK 2
  • Cyclin D/CDK 4,6
  • Cyclin E/CDK 2
  • Cyclin B/CDK 1 (correct)

    • What is the initial step in the ubiquitin-mediated proteasome degradation of cyclins?

    <p>A polyubiquitin chain is added to the cyclin.</p> Signup and view all the answers

    What is the primary function of the proteasome in protein degradation?

    <p>It cleaves proteins into amino acids.</p> Signup and view all the answers

    What differentiates Type 2 nuclear receptors from Type 1 nuclear receptors?

    <p>Type 2 receptors are ligand-dependent.</p> Signup and view all the answers

    Which component of the nuclear receptor structure is responsible for ligand specificity?

    <p>Ligand binding domain</p> Signup and view all the answers

    What is the role of coactivators in nuclear receptor function?

    <p>They enhance gene transcription.</p> Signup and view all the answers

    Which of the following statements about orphan receptors is true?

    <p>Their function remains poorly understood.</p> Signup and view all the answers

    What mechanism allows steroid hormones to interact with nuclear receptors?

    <p>Conformational changes and translocation to the nucleus.</p> Signup and view all the answers

    Which of the following is a characteristic of Selective Estrogen Receptor Modulators (SERMs)?

    <p>They can act as agonists or antagonists depending on the tissue.</p> Signup and view all the answers

    What is the primary role of the N-terminal domain in nuclear receptors?

    <p>It contains phosphorylation sites and is variable.</p> Signup and view all the answers

    How do Type 1 nuclear receptors initially interact with their ligands?

    <p>They bind to the ligand before release from the carrier.</p> Signup and view all the answers

    What is the initial step in the apoptosis process?

    <p>Signal sent from damaged cells</p> Signup and view all the answers

    What role do BCL-2 proteins play in the apoptosis pathway?

    <p>Prevent mitochondrial membrane permeability</p> Signup and view all the answers

    Which enzyme is responsible for converting Procaspase 9 into active caspase 9?

    <p>Apoptotic Protease Activating Factor-1</p> Signup and view all the answers

    What occurs after the mitochondrial membrane becomes permeable?

    <p>Release of cytochrome c</p> Signup and view all the answers

    What is a primary function of caspases in the apoptosis process?

    <p>To initiate nuclear break-up</p> Signup and view all the answers

    What is the consequence of immune cell targeting in apoptosis?

    <p>Engulfment of the cell</p> Signup and view all the answers

    Which of the following signals can initiate apoptosis?

    <p>Death domain receptors</p> Signup and view all the answers

    What is one of the key features of apoptosis?

    <p>Programmable cell death</p> Signup and view all the answers

    What is the primary purpose of the G1 phase in the cell cycle?

    <p>Cell growth and metabolism</p> Signup and view all the answers

    Which phase follows DNA synthesis in the cell cycle?

    <p>G2</p> Signup and view all the answers

    Which type of cells is known for having a high ability to divide?

    <p>Adult stem cells</p> Signup and view all the answers

    What experimental evidence supports the hypothesis of cellular factors controlling the cell cycle?

    <p>Fusion of cells at different stages</p> Signup and view all the answers

    During which phase does the chromatin condense and the nuclear membrane dissolve?

    <p>Prophase</p> Signup and view all the answers

    What occurs in the G2 phase of the cell cycle?

    <p>Cell growth and organelle replication</p> Signup and view all the answers

    Which type of cells exhibit an inability to divide?

    <p>Nerve cells</p> Signup and view all the answers

    What is the result of fusing a mitotic cell with a G1 or G2 cell according to the hypothesis of Johnson & Rao?

    <p>Cell stops until the other phase catches up</p> Signup and view all the answers

    What is the function of relay points in component systems?

    <p>To integrate multiple signals into a cohesive response</p> Signup and view all the answers

    Which statement best describes the relationship between hosts and pathogens?

    <p>Pathogens adapt to overcome host defenses while hosts adapt to enhance defense mechanisms.</p> Signup and view all the answers

    How do bacterial quorum sensing and host communication systems interact?

    <p>Bacteria communicate through hormone recognition and hosts have hormone receptors to sense them.</p> Signup and view all the answers

    What is a key characteristic of the release of signaling molecules in eukaryotic signal transduction?

    <p>Signals are stored in vesicles and released by exocytosis for rapid action.</p> Signup and view all the answers

    Which of the following statements about the speed of response in eukaryotic signal transduction is true?

    <p>Fast responses are typically mediated through peptide hormones and catecholamines.</p> Signup and view all the answers

    What is a common property of signaling molecules in eukaryotic cells?

    <p>They typically have a short half-life, lasting seconds to minutes.</p> Signup and view all the answers

    What occurs after the interaction of a signaling molecule with a target cell?

    <p>There is a change in cell behavior, potentially involving gene regulation.</p> Signup and view all the answers

    What role does the removal of signals from target cells play in eukaryotic signal transduction?

    <p>It helps to reset the target cell's state for future signaling.</p> Signup and view all the answers

    What are the secondary messengers produced by the cleavage of phosphorylated inositol by PI specific phospholipase?

    <p>Cytosolic Inositol Triphosphate and Diacyl glycerol</p> Signup and view all the answers

    What is the primary function of activated Protein Kinase C in the signaling pathway?

    <p>To phosphorylate serine and threonine residues</p> Signup and view all the answers

    Which type of receptor can auto-phosphorylate itself?

    <p>Receptor Tyrosine Kinases</p> Signup and view all the answers

    What initiates the activation of Ras in the signaling cascade?

    <p>Binding of GTP</p> Signup and view all the answers

    Which one of these downstream effects is mediated by activated Ras?

    <p>Activation of the MAP kinase pathway</p> Signup and view all the answers

    What role do Guanine Exchange Factors (GEFs) play in Ras activation?

    <p>They facilitate the conversion of Ras from inactive to active form</p> Signup and view all the answers

    What is the result of receptor dimerization in receptor tyrosine kinases?

    <p>Stimulated autophosphorylation</p> Signup and view all the answers

    What is a major function of the signaling pathways mediated by receptor tyrosine kinases?

    <p>Regulation of cell proliferation</p> Signup and view all the answers

    What defines receptor tyrosine-linked kinases compared to receptor tyrosine kinases?

    <p>They lack kinase activity and depend on other molecules for phosphorylation</p> Signup and view all the answers

    Which cellular response is NOT typically associated with receptor tyrosine kinase pathways?

    <p>Calcium release from smooth ER</p> Signup and view all the answers

    Study Notes

    Cell Communication and Signal Transduction Pathway

    • Cells communicate with each other and the environment.
    • Signals are sent through the cell to regulate function.
    • Quorum sensing in bacteria is defined.
    • General steps in signal transduction are explained.
    • Proteins involved in different types of cellular signaling are explained.

    Signaling Types

    • External signal from environment: Response to stimuli (temperature, light, pressure), foreign cells (bacteria, viruses), and chemical/antigens
    • External signal from the organism: Hormones
    • Cell-cell contact
    • Internal signal from the cell: Autocrine, signal cascades

    Bacteria – 2 Component System

    • All bacteria have 2-component signaling systems.
    • Sensor: Histidine protein kinase
    • Effector: Response regulator (aspartic acid protein kinase)
    • Kinases: Proteins which transfer a phosphate anion to another protein.
    • Phosphorylation: Adding a phosphate anion to a protein.
    • Phosphatases: Proteins which remove a phosphate from another protein.

    Bacteria – 2 Component System Steps

    • Receive input stimulus (osmolarity, pH, temperature, antibiotics).
    • Autophosphorylation of Sensor (histidine kinase).
    • Transfer of phosphate to Response Regulator (aspartic acid).
    • Response - Gene regulation (turn on or off).
    • Dephosphorylation of effector (turn off signal).
    • Phosphorylated aspartate is unstable

    Prokaryotic Communication

    • Bacteria communicate with other bacteria to effectively invade host tissue.
    • Bacteria may need to produce an enzyme to break down host defense proteins to gain a foothold.
    • The enzyme must be effective against the host, requiring the bacteria to know how many bacteria are present.

    Bacteria Quorum Sensing

    • Cell density-dependent response.
    • Bacteria sense the presence of enough bacteria to activate relevant genes. Bacteria are sending out an autoinducer (AI).
    • The AI migrates back into the bacteria, and the concentration of AI increases as the bacteria grow.
    • When a trigger point occurs, all bacteria activate a gene to produce a response or attack the host. (e.g. LasA in cystic fibrosis patients)

    Quorum Sensing

    • Bacteria transcribe Gene A to make protein A.
    • Protein A creates and releases AI into the host environment.
    • As the bacterial colony density increases, the concentration of AI increases and diffuses back into the bacteria.
    • Eventually, the high concentration of AI turns on other genes to produce effective responses needed to attack host tissue.

    Prokaryotic Cell Communication

    • Bacteria use 2-component signaling and Quorum Sensing in an integrated fashion.
    • Component systems can have several relay points.
    • Bacteria receive multiple signals simultaneously (pH changes, temperature, host immune responses).
    • All signals are integrated to create a response to survive.

    Host-Pathogen Relationship

    • Hosts and pathogens are in a constant evolutionary state.
    • As one evolves to survive, it puts selective pressure on the other to evolve and survive.
    • A bacteria may evolve to enter the host cell better.
    • The host will respond by evolving to prevent bacteria entry.
    • The host may evolve to recognize the bacteria faster.
    • The bacteria may evolve to disguise itself to avoid recognition.
    • The cycle continues; constant communication between the host cells, pathogen and the environment.

    Bacterial Quorum Sensing Communication

    • Bacteria may communicate with the host system through hormone recognition.
    • Conversely, the host may sense bacteria through hormone receptors.

    Eukaryotic Signal Transduction

    • General Steps: Synthesis of signaling molecule, release of signaling molecule by the signaling cell, transport of signal to target cell, interaction of signal with target cell (membrane, cytosol, nucleus), change in cell behavior (up or down gene regulation), removal of signal from target cell.

    Eukaryotic Signal Transduction Properties

    • Fast response: Mediated through peptide hormones and catecholamines; fully active stored in vesicles; short half-life (seconds-minutes)
    • Slow response: Mediated through steroid and growth hormones; synthesis is slow; stored in an inactive precursor form; released by diffusion; travels a longer distance; slower degradation half-life (hours-days).

    Eukaryotic Cell to Cell Signal Transduction

    • Three Primary Mechanisms: Contact (signaling cell directly contacts target cell, major mechanism of immune system), Gap Junctions (signaling across specialized channels-connexons), Secretion (release of signals into interstitial/bloodstream fluid).

    Eukaryotic Signal Transduction

    • Types of Secretion: Endocrine (cell remote from target cell-hormones), Paracrine (adjacent cells-neurotransmitters, immune response), Autocrine (target produces its own signaling molecule-growth factors, community effect).

    Exocytosis

    • Vesicles fuse with plasma membrane and release proteins/signal molecules.
    • Two secretory pathways: Constitutive (continuously producing proteins, etc., for normal functioning), Regulated (specialized process of secretory cells; selecting proteins for release through clathrin-coated vesicles).

    Signal Transduction

    • Various types of signal transduction pathways are present in higher organisms (G-Protein Coupled Receptors, Receptor Tyrosine-Linked Kinases, Receptors with Intrinsic Enzymatic Activity). This includes receptor tyrosine kinases (receptor tyrosine phosphatases, receptor serine/threonine kinases, receptor guanylate cyclases).
    • Includes Nuclear Receptors and Apoptosis

    Signal Transduction and Secondary Messengers

    • Signaling cascades involve a relay of protein activation (phosphorylation).
    • Many signaling cascades use secondary messengers, including cAMP, lipids (DAG), and calcium.

    G-Protein Coupled Receptors

    • Membrane-bound receptors linking G-proteins to outside signals.
    • Ligand binding domains on the ectoplasmic face; cytosolic domains activating G-proteins.
    • Examples: Beta-Adrenergic Receptor, Rhodopsin
    • Seven membrane-spanning regions, N-terminal segment on exoplasmic face, C-terminal segment on cytosolic face.
    • Includes light-activated receptors, odorant receptors, hormone/neurotransmitter receptors (e.g., GABA).

    G-Proteins

    • Proteins which bind GTP and GDP.
    • Act as on/off switches; inactive (GDP), active (GTP).
    • Activate downstream proteins and interact with membrane receptors.

    Note

    • Terminology should be clear-distinguish receptors from ligands/proteins that interact with the receptor.
    • Keep G-Protein terms separate from receptor terms.

    Phosphatidyinositol Signaling

    • PI is phosphorylated twice to produce PI(4,5)P2.
    • PI-Phospholipase cleaves the phosphorylated inositol to produce secondary messengers, including IP3 and DAG.
    • IP3 is a ligand for Calcium channels on the smooth ER, causing calcium release, and DAG activates Protein Kinase C.

    Enzymatic Activity

    • Receptor Tyrosine Kinases: Receptors that can auto-phosphorylate and pass signals to cell effectors.
    • Receptor Tyrosine-Linked Kinases: Receptors lacking kinase activity, depending on another molecule for phosphorylation and passing signals to effectors. Linked to Tyrosine Kinases.

    Intrinsic Enzymatic Activity

    • Receptor Tyrosine Kinases (RTKs): Transmembrane protein receptors with ligand binding domains (ectoplasmic) and activating domains (cytoplasmic).
    • Auto-phosphorylation transfers phosphates to substrate. Subsequent cascade effects activate downstream proteins (e.g., Growth Factor Receptor).

    Receptor Tyrosine Kinases

    • RTK signaling pathways regulate gene expression via effects on cell proliferation, differentation, survival, and cellular metabolism.
    • RTKs transmit a growth signal, activating Ras, a GTPase protein that transmits the signal to downstream components.

    Effector: Activation of Ras

    • Ras is a proto-oncogene mediating growth hormone mitogenic stimuli.
    • It's a membrane-anchored protein.
    • Inactive Ras is bound to GDP, while active Ras is bound to GTP.
    • Active Ras activates Raf, activating the MAP kinase pathway, leading to cell proliferation.

    Activation of Ras

    • GEFs (Guanine Exchange Factors) replace GDP with GTP to activate Ras.
    • GAPs (GTPase Activating Proteins) enable Ras to hydrolyze GTP to GDP (inactivating Ras).

    MAP Kinase Pathway

    • MAP Kinase cascade uses signal transduction through several Protein Tyrosine Kinases.
    • Ras activates Raf. Multi-step phosphorylation cascade of downstream protein kinases.
    • Gene expression is eventually activated by a transcription factor via MAP kinases.

    Nuclear Receptors

    • Type 1: Nuclear receptors bound to HSP in the cytoplasm/nucleus. Ligand-dependent, activate transcription (e.g., steroid, estrogen, progesterone, glucocorticoid receptors).
    • Type 2: Nuclear receptors located on the gene to repress genes. Ligand-dependent transcription (e.g., thyroid, retinoid, Vitamin D receptors).

    Receptor Domain

    • DNA Binding Domain: Highly conserved region.
    • Ligand Binding Domain: Provides specificity to the ligand.
    • N-Terminal Domain: Variable; contains phosphorylation sites, activates co-activators or co-repressors.

    Type I – Nuclear Receptors

    • Steroid binding to the receptor causes conformational changes and its release from the carrier. Translocation to the nucleus; Receptor/ligand complex dimerization; DNA interaction; Gene Transcription.

    Nuclear Receptors – Steroid #1 and #2

    • Receptor-ligand complex binding, coactivator recruitment, DNA binding, and transcription are the steps for both steroid #1 and #2.

    Selective Estrogen Response Modulators (SERMS)

    • SERMs are receptor modulators that can be agonists or antagonists in tissues.
    • Examples include Raloxifene (bone tissue agonist), and Tamoxifen (breast cancer antagonist).

    Type II Receptors (Thyroid)

    • Translocation to nucleus. Binding to receptors. Remove co-repressor signal. Activate gene transcription.

    Apoptosis

    • Signaling pathway that leads to cell death: Controlled cell-death pathway, normal development (web removal), bacterial/viral infection (mediated by immune system), DNA damage and mutation.

    Apoptosis – Initiation

    • External through "Death Domain" receptors.
    • Internal through stress detection.
    • Targeting by an immune cell.
    • Activation of caspases (cysteine/aspartic acid cleavage proteases); cell shrinkage; nuclear breakup; surface bleb formation; engulfment by phagocytes.

    The Mitochondria and Apoptosis

    • Internal cellular damage causes stress, sensed by the endoplasmic reticulum (RER; affects protein synthesis).
    • Signal sent to activate proapoptotic proteins (Bax, Bad).
    • Activation of Bax/Bad causes mitochondrial membrane permeability, releasing cytochrome c (a messenger).
    • Cytochrome c triggers caspase-9 activation, activating the procaspases, which in turn activates downstream effector caspases.

    Receptor-mediated Apoptosis Pathway

    • Tumor Necrosis Factor (TNF) binds to its receptor, activating death domains to recruit adaptor proteins FADD and TRADD.
    • This provides caspase-8 activation.
    • Caspase-8 cleaves caspase-3, which is the major executioner caspase targeting the nucleus.

    Integration of Signals

    • Eukaryotes integrate simultaneous signals.
    • Convergence: Multiple signals use the same effector.
    • Divergence: Similar ligand triggers different pathways based on tissue/receptor type or other signals
    • Crosstalk: Different signaling cascades communicate. Multiple downstream events can arise from one single signaling event.

    p53 Normally Inactive

    • p53 is a transcription factor normally inactive.
    • Good growth: Ubiquitin-mediated degradation by MDM2.
    • DNA damage: Activation of p53 and p21 production. MDM2 can no longer target p53 leading to cell-cycle arrest. p21 blocks cyclin/CDK from being active.

    Cell Division Cycle Mutants: Yeast

    • Researchers create mutants in yeast using temperature sensitivity as a marker (grow at 25°C but not 35°C)
    • Shifting growth temperatures from high to low indicates if mutations disrupt the cell cycle.

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