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HY Cell Bio 2

Day 11

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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