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HY Cell Bio 2
Day 11
| Question | Answer |
|---|---|
| Phosphorylate target proteins to drive the cell cycle | Cyclins + cyclin-dependent kinases (CDKs) |
| Responsible for degrading cyclins when their cell-cycle specific job is complete | Ubiquitin protein ligase |
| Name 3 tumor suppressor genes that bind to and inactivate cyclin-CDK complexes | p21, p27, and p57 |
| Which tumor suppressor gene controls the activity of p21, another tumor suppressor gene? | p53 |
| Which complex leads to phosphorylation of the Rb protein? | Cyclin D/CDK4 |
| What does phosphorylation of the Rb protein do? | Inactivates Rb protein, so it is released from transcription factor E2F--> cell is free to transcribe/synthesize components needed for progression thru S phase. |
| What components are synthesized for progression thru S phase (enabled by E2F)? | cyclin E, DNA polymerase, thymidine kinase, and dihydrofolate reductase. |
| Which complex allows the cell to progress into S phase? | Cyclin E/CDK2 |
| Which complex allows the cell to progress to prophase of mitosis? | Cyclin A/CDK2 |
| Which complex is responsible for breaking down the nuclear envelope (nuclear lamin breakdown) and initiation of mitosis? What activates this complex? | Cyclin B/CDK1 (B for Breakdown); activated by cdc25 |
| Assists in proper folding and transport of polypeptides across the ER, Golgi, and beyond. | Chaperones |
| Chaperones that are induced by stress and rescue shock-stressed proteins from misfolding. | Heat shock proteins (hsp 70, hsp 90) |
| Facilitate degradation if folding of protein does not take place properly | Chaperones |
| Heat shock protein that targets damaged proteins for degradation | Ubiquitin via ubiquitin-proteasome complex (also marks p53, oncoproteins, protein kinases, immune system cell surface receptors, and CD molecules for degradation) |
| What protein is involved in transporting an endocytosed vesicle from the plasma membrane to the endosome? | Clathrin |
| What molecule targets proteins in the endoplasmic reticulum for lysosomes? | Mannose-6-phosphate |
| What protein allows the cargo receptor to associate with the clathrin molecule? | Adaptin |
| What protein pinches off the clathrin coated vesicle to cause endocytosis? | Dynamin |
| How is clathrin recycled? | Endocytosed vesicle is uncoated so clathrin can be reused. |
| Describe the pathogenesis of how having a mutant LDL receptor predisposes an individual to a higher risk of dying prematurely from a myocardial infarction. | Mutant LDL receptor lacks the coated-pit binding site, but retains a functioning LDL-binding site. As a result, cells with mutant receptors are able to bind LDL normally but are unable to ingest it. |
| Which intermediate filament is responsible for supporting the cellular membranes and keeping certain organelles fixed within cytoplasm. | Vimentin |
| Which intermediate filament is a structural component of connective tissue (fibroblasts, leukocytes, endothelium)? | Vimentin |
| Which intermediate filament is a structural component of muscle cells (smooth, skeletal, and heart)? | Desmin |
| Which intermediate filament is a structural component of epithelial cells (keratin in desmosomes and hemidesmosomes)? | Cytokeratin |
| Which intermediate filament is a structural component of astrocytes, Schwann cells, and other neuroglia? | Glial fibrillary acid proteins (GFAP) |
| Which intermediate filament is a structural component of neurons? | Peripherin |
| Which intermediate filament is a structural component of axons within neurons? | Neurofilaments (Low, Medium, and High molecular weight) |
| Which intermediate filament is a structural component of the nuclear envelope and the DNA within it? | Nuclear lamins (A, B, C) |
| Mutations of nuclear lamins are associated with which two diseases? | Progeria (advanced aging disease) and muscular dystrophy |
| Transmembrane receptors that bind to an extracellular ligand then intracellulary transfer a phosphate group from ATP to selected tyrosine side chains on specific cellular proteins including itself (autophosphorylation). | Tyrosine kinase receptor |
| What is the first step in the signaling cascade that is intitiated by tyrosine kinase receptors? | Autophosphorylation |
| What kind of transmembrane protein is PDGF and other growth factors? | single-pass transmembrane protein |
| Which receptors have 2 alpha subunits (bound by disulfide bonds) that bind extracellular ligand and two beta subunits that are responsible for tyrosine kinase activity? | Insulin and IGF-1 receptors |
| What happens in this stage of skin healing?: 0-3 hours | Hemorrhage and clotting |
| What happens in this stage of skin healing?: 12-24 hours | Acute inflammation (PMNs) |
| What happens in this stage of skin healing?: 2-4 days | Macrophage infiltration and epithelial cell migration (epithelization) |
| Why should a surgical bandage be kept on for the first 24 hours? | Allows important process of epithelization to take place uninterrupted. |
| What happens in this stage of skin healing?: 3-5 days | Granulation tisse (esp at wound edges) |
| What type of collagen is seen in early granulation tissue? | Type III (bloody collagen) |
| What happens in this stage of skin healing?: months after injury | Collagen production (granulation is type III initially, but later is type I=the strong type for scars) |
| Loss of what cell signals will initiate apoptosis? | Growth factors |
| Presence of what "environmental" cell signal will initiate apoptosis? | Stress |
| What gene triggers apoptosis when DNA damage is present and the DNA repair process fails? | p53 (this is why p53 mutation is implicated in many cancers) |
| Which cytokine triggers apoptosis? | TNF |
| How do cytotoxic T cells lead to apoptosis? | Insert granzyme B into cells which leads to activation of caspases |
| ______ proteases execute apoptosis and have _____ protease that cleaves after aspartic acid residues. | Caspases; cysteine |
| Which apoptotic pathway induces cell death via activation of a cell surface death receptor (another name for this pathway is the Death Receptor Mediated pathway)? | Extrinsic pathway |
| Which apoptotic pathway induces cell death via increased mitochondrial permeability? | Intrinsic pathway |
| How does increased mitochondrial permeability lead to apoptosis? | Causes release of pro-apoptotic molecules into the cytoplasm (normally no communication between mitochondrial death enzymes and cytoplasm) |
| Fas (CD95) and Fas ligand belong to which apoptotic pathway? | Extrinsic pathway (Death Receptor Mediated) |
| The Fas-associated death domain (FADD) binds inactive __________ which cleaves and activates other pro-caspases which leads to the apoptotic proteolytic cascade. | caspase 8 (caspase 10 in humans) |
| Which cascade is the pathway used in selection of T cells? | Apoptotic proteolytic pathway |
| Which protein can bind to and inhibit cleavage of pro-caspase 8 thereby inhibiting apoptosis? | FLIP protein |
| Which class of proteins regulate apoptosis in the intrinsic pathway (mitochondrial)? | Bcl-2 |
| Which Bcl-2 proteins and anti-apoptotic? | Bcl-2 and Bcl-x (Bcl-2 is analagous to Ced9) |
| Which Bcl-2 proteins are pro-apoptotic? | Bak, Bax, and Bim (the apoptotic thugs) |
| When the cell undergoes stress,w hich proteins are lost from the mitochondrial membrane? What are they replaced with? | Bcl-2 and Bcl-x are lost; they are replaced with Bak, Bax, and Bim. This causes increased mitochondrial permeability. |
| Which substances are leaked as a direct result of increased mitochondrial membrane permeability? | Cytochrome c (caspase activating protein) and AIF (apoptosis inducing factor) |
| Which complex in the intrinsic pathway is responsible for activating caspase 9? | Cytochrome c bound to Apaf-1 (apoptosis activating factor-1; homologous to Ced-4) |
| What is the function of AIF in the intrinsic pathway? | AIF (apoptosis inducing factor) binds to and neutralizes various inhibitors of apoptosis which means that apoptosis is no longer inhibited |
| What factor is expressed by healthy cells to prevent phagocytosis? | CD31 |
| What drugs act on microtubules? | Griseofulvin, -bendazoles, vincristine/vinblastine, -taxels, and colchicine |
| What findings are assoc'd with Ehler's Danlos syndrome? | Stretchy skin, hypermobile joints, increased bleeding tendency, and Berry aneurysms |
| Which arachidonic acid product causes the following effect?: Increased bronchial tone | Leukotrienes, thromboxane |
| Which arachidonic acid product causes the following effect?: decreased bronchial tone | Prostacyclins and prostaglandins |
| Which arachidonic acid product causes the following effect?: increased platelet aggregation | Thromboxane |
| Which arachidonic acid product causes the following effect?: Decreased platelet aggregation | Prostacyclins |
| Which arachidonic acid product causes the following effect?: Increased uterine tone | Prostaglandins |
| Which arachidonic acid product causes the following effect?: Decreased uterine tone | Prostacyclins |
| Which arachidonic acid product causes the following effect?: Increased vascular tone | Thromboxane (only goal in life is to make a clot, so it vasoconstricts to keep all that bloodflow from messing up its beautiful masterpiece) |
| Which arachidonic acid product causes the following effect?: Decreased vascular tone | Prostaglandin, prostacyclins |
| What are the 2 most abundant substances in the plasma membrane? | Cholesterol and phospholipids |
| What provides the structural framework for DNA and the nuclear envelope? | Lamins A, B, and C |
| What drug inhibits lipoxygenase? | ZiLEUton |
| Which drugs inhibit Leukotrienes LTC4, LTD4, LTE4)? | ZafirLUKast and monteLEUKast |
| Which drugs inhibit cyclooxygenase? | NSAIDs, acetaminophen, COX-2-i, and aspirin |
| What process is mediated by COX-1? | Production of protective prostaglandins in gastric mucosa (this is why we have selective COX-2-i that spare the gastric mucosa) |
| What process is mediated by COX-2? | Inflammation |
| What enzyme in the arachidonic acid pathway is inhibited by corticosteroids? | Phospholipase A2 |
| Name 3 inhibitory actions of corticosteroids. | 1. Inhibits collagen synthesis 2. Inhibits phospholipase A2 3. Inhibits apoptosis |
| What is the precursor to arachidonic acid that is acted upon by phospholipase A2? Where is it found? | Phosphatidylinositol, a lipid found in membrane |
| Which cyclooxygenase inhibitor is peripherally inactivated so it only acts centrally (no anti-inflammatory properties)? | Acetaminophen |
| Which arachidonic acid product is important for renal blood flow (be specific)? | PGE2 |
| What drug should be used in patients who are allergic to aspirin? | Clopidigrel |
| Leukocyte extravasation: What is rolling mediated by? | Selectins (E and P) |
| Leukocyte extravasation: What is tight binding mediated by? | Integrins (ICAM-1) |
| Leukocyte extravasation: What is diapedesis mediated by? | PECAM-1 |
| Leukocyte extravasation: What is migration mediated by? | Chemotactic factors: IL-8, LTB4, C5a, Kallikrein (clean up in "aisle"/IL-8, neutrophils get there B4 everything else) |
| How are molecules transported into the nucleus? | Nuclear localization signals: rich in Lysine, Arginine, and Proline (come into the nucleus and sit on my LAP) |
| What histologic features are seen in apoptotic liver cells? | Cell shrinkage, nuclear shrinkage and basophilia (pyknosis), membrane blebbing, pyknotic nuclear pigmentation, nuclear fading, formation of apoptotic bodies |
| Rb mutations are associated with which 2 cancers? | Retinoblastoma and osteosarcoma |
| If you see Nissl bodies, what structure are you looking at? | Dendrites (Nissle bodies are NOT seen on axons) |
| People taking a LOT of meds will have increased amounts of which component of the cell? | Smooth endoplasmic reticulum (SER): resonsible for detoxification of drugs and poisons |
| Terminally divided cells (neurons, skeletal and cardiac m, and RBCs) are stuck in which phase of the cell cycle? | G0 (the resting state); they are permanent cells |
| Which AA are modified by the Golgi? | 1. Asparagine 2. Serine 3. Threonine |
| I-cell disease looks like what other set of diseases? | Mucopolysaccharidoses (Hunter's, Hurler's, and Scheie's) |
| Which drug hyperstabilizes microtubules, preventing the cell from completing mitosis? | Paclitaxel (used to treat breast cancer) |
| How do ciliated cells communicate and coordinate their efforts? | Via gap junctions |
| What are the characteristics of the 4 different types of collagen? | Type 1= Strong (bone), Type 2= Slippery (cartilage), Type 3= Bloody (vascular tissues), Type 4= BM (also basal lamina) |
| What is the most abundant AA in the collagen molecule? | GLYCINE |
| To be able to fold into a triple helix, every 3rd AA in each alpha chain must be ______. | GLYCINE |
| Where do hydroxylation and glycosylation of collagen precursors occur? | In the RER |
| Defects in what step of collagen synthesis produces the joint laxity, loose skin, and easy bruisability seen in patients with Ehler's Danlos? | Proteolytic processing step: Defective cleavage at N- and C-terminals yields the formation of more soluble collagen that does not properly cross-link with other collagen molecules. |
| What type of collagen is defective in Ehler's Danlos? | Type 3 (3 looks like a backwards E) |
| What type of collagen is defective in Osteogenesis Imperfecta? | Type 1 (1 looks like an I for Imperfecta) |
| What type of collagen is defective in Alport's syndrome? | Type 4 (BM problem; type 4 is on the floor) |
| Inter-chain cross links involving which AA are responsible for the stretchiness of elastin fibers in the alveolar walls of the lung? | Lysine (also note that elastin is rich in non-glycosylated proline and glycine) |
| What 3 factors are responsible for the increased vascular permeability and vasodilation seen with fluid exudation? | Histamine, serotonin, and bradykinin |
| What enzyme is responsible for the remodeling process in the resolution phase of inflammation? | Metalloproteinases |
| What two substances are given as supplements in patients undergoing wound healing? | Zinc (req'd by metalloproteinases) and vitamin C (necessary for fibrosis) |
| Which poison has a nearly identical effect to that of the cardiac glycosides like digoxin? | Ouabain (inhibits the Na/K ATPase pump by binding to the K site) |
| The tyrosine kinase receptor can go through an alternative pathway that is identical to which 7-pass transmembrane receptor? | Gq; activates phospholipase C (remember 7-pass transmembrane receptor=G Protein coupled receptor) |
Created by:
sarah3148
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