Transcript 슬라이드 1
Final exam (6-18) 학과 이름 학번 Chapter 13 Facilitated diffusion involves the movement of molecules in the direction determined by their relative concentration inside and outside of the cell without external energy provided. There are two classes of proteins that mediate facilitated diffusion – channel proteins make open pores through the membrane, allowing the free diffusion of any molecules of the appropriate size and charge, (A: carrier ) proteins bind specific molecules, then undergo conformational changes that allow the molecule to pass through the membrane. 1. 옆 그림은 intestinal epithelial cells이 intestine 으로부터 circulation으로 glucose 를 흡수하여 전달하는 과정을 묘사하고 있다. 1.Glucose is uptaken from the intestinal lumen by a mechanism so-called active transport driven by (B:ion gradient or Na+ ion gradient 그냥 ion혹은 Na+도 정답 처리하였읍니다) 2. 2. As a whole, (C: Na+-K+ pump) found on both apical and basolateral membrane domains drives this glucose transport system by establishing (B) across the plasma membrane. (D: Receptor-mediated endocytosis- 그냥 endocytosis는 정답이 아닙니다) provides a mechanism for the selective uptake of specific macromolecules. The macromolecules to be internalized first bind to specific cell surface receptors. Most of these receptors are concentrated a specialize regions of the plasma membrane called clathrin-coated pits. The uptake of cholesterol, especially low-density lipoprotein, by mammalian cells has provided a key model for understanding (D) Chapter 14 Most animal cells in tissues are embedded in an (A: extracellular matrix), which consist of a variety of secreted proteins and polysaccharide. The major structural protein of (A) is (B: collagen). (B) is characterized by the formation of triple helices, and (B) contains unusual amino acids such as hydroxyproline. The fibrous structural proteins of (A) are embedded in gels formed from polysaccharides called (C: glycosaminoglycans or GAG), which consist of repeating units of disaccharides. Importantly, these sugars are (D: negative-charged). Thus, they bind positively charged ions and trap water molecules to form hydrated gels, thereby providing mechanical support to (A). (E: Tight junction) prevent the free passage of molecules between epithelial cells and separate the apical and basolateral domains of epithelial cell plasma membranes. (F: gap junction) are open channels connecting the cytosols of adjacent animal cells, which synchronize adjacent cells metabolically and electronically. Chapter 15 (A: eicosaniods) are synthesized from phospholipids that function locally in para and autocrine signaling. (A) stimulates a variety of responses in the target cells including blood platelet aggregation and inflammation. (B: steroid hormone), thyroid hormone, or vitamin D3 are small hydrophobic molecules that diffuse across the plasma membrane and bind to intracellular receptors. (C: nitric monooxide or NO or CO or carbon monooxide) is a simple gas acting as a major paracrine signaling molecule in the nervous and immune system. The major intracellular target of (C) is guanylyl cyclase, which induces a variety of responses including the dilation of blood vessel. Many hormones including epinephrine binds to their receptors, which activates guanine nucleotidebinding proteins so-called (D: G protein). More than a thousand such (D)-coupled receptors have been identified including the receptors for neurotransmitters, neuropeptides and peptide hormones. In addition, the (D)-coupled receptor family includes a large number of receptors responsible for smell, sight, and taste. Activated (D) increases an intracellular level of (E: cyclic AMP or cAMP) by stimulating an enzyme called (F: adenylyl cyclase). (E) is then degraded by a phosphodiesterase E E E E (E) activates (G: cAMP-dependent protein kinase / protein kinase A or PKA ) as shown in the figure, and the activated (G) regulates glycogen metabolism or translocates into the nucleus, leading to expression of a variety of genes by phosphorylating a transcription factor, CREB. E. A. 1. The cytoplasmic domains of the receptors for most growth factors including EGF, PDGF, NGF, and insulin are (A: protein-tyrosine kinases – tyrosine kinase도 정답으로 채 점하였읍니다), which phosphorylate each other (so-called autophosphorylation) when the two receptors are dimerized upon ligand binding. On the contrary, the receptors for many cytokines act in association with nonreceptor (A) such as JAK. 2. Various downstream signaling proteins containing SH2 domains bind to specific phosphotyrosine-containing peptides of the activated receptors. E. 2.1. Phospholipase C-γ (PLC-γ), one of those SH2-containing protein, is activated upon binding to the cytoplasmic domains of the receptor, stimulating the hydrolysis of phosphatidylinositol 4,5-bisphosphate (PIP2) into (B: diacylglycerol or GAG) and (C: inositol 1,4,5-triphosphate / IP3). (B) activates protein kinase C and (C) mobilizes calcium ions, so PIP2 hydrolysis triggers a two-armed cascade of intracellular signaling. 2.2. PIP2 is converted into PIP3 by (D: PI 3-kinase) which is activated upon binding to growth factor receptors using its SH-2 domain. A key target of PIP3 is a protein serine/threonine kinase called Akt, which phosphorylates a variety of proteins. 2.3. MAP kinase signaling from various growth factor receptors are highly conserved in evolution. An important intermediate molecule (E: Ras), a GTP-binding protein, is activated and elicits a array of protein kinase cascades, ultimately leading to expression of genes involved in cell growth and survival. DNA damage to apoptosis One important role of apoptosis is the elimination of damaged cells Severe DNA damage induced by UV light or ionizing radiation is recognized by a protein complex containing ATM (or ATR). These protein kinases are then activated and phosphorylate (A). Phosphorylated (A) is stabilized from proteasomal degradation and induces a array of genes including BH3-only proapoptotic proteinsencoding genes. BH3-only apoptotic proteins activate proapoptotic multidomain proteins (e.g. bax) by sequestering antiapoptotic proteins (e.g. Bcl-2) and the released bax molecules form pores in the mitochondrial outer membrane, leading to release of (B). (B) binds to apoptosome and thus a initiator caspase (caspase-9) is activated. A A A A: B p53 B: cytochrome C What are key targets of the effector caspases to induce DNA fragmentation (an inhibitor of a DNase), nucleus break-up (D), and cell shrinkage or cell membrane blebbing (E) C: nuclear lamin or lamin (nuclear lamina ) 그냥 lamina는 오답 D: cytoskeletal proteins or cytoskeleton Cell renewal Most differentiated cells do not proliferate but can be replaced via the proliferation of (E: stem cells or adult stem cells). (E) divide to produce one daughter cell that remains a (A) and another that divides and differentiates. (E) have been identified in a wide variety of adult tissues including hematopoietic system and skin. Mammals have been cloned by (F: somatic cell nuclear transfer) in which the nucleus of an adult somatic cell is transplanted into an enucleated egg. This opens the possibility of therapeutic cloning in which embryonic stem cells would be derived from a cloned embryo and used for transplantation therapy of the donor of the adult nucleus. Eukaryotic cell cycles are divided into four discrete phases: M, G1, S, G2. A: CDK / cyclin-dependent kinase B: cyclin (C) (C) (C) (D) (C) The coordination between different phases of the cell cycle is dependent on a series of (C: cell cycle checkpoints or check points) that prevent entry into the next phase of the cell cycle until the events of the preceding phase have been completed or when unreplicated or damaged DNA is detected. The proliferation of most animal cells is regulated at a decision point at the last G1 phase by the extracellular growth factors. What is called? (D: restriction point) Cell signaling에 중요한 Second messengers를 쓰시요. (2점씩). Ca2+ cAMP cGMP IP3 PIP2 Diacylglycerol (DAG) Chapter 15 Properties of cancer cells The proliferation of most normal cells is controlled by (A: growth factors) whereas many cancer cells have reduced requirement for (A), contributing to the unregulated proliferation of cancer cells. In some cases, cancer cells produce (A) that stimulate their own proliferation (socalled autocrine growth stimulation). Cancer cells are also less stringently regulated than normal cells by (B: cell-cell and cell-matrix interaction/contact). Thus, most cancer cells are less adhesive and this property contributes to the ability of malignant cells to invade adjacent tissues and metastasize. Another general characteristic of most cancer cells is that they are defective in (C: differentiation). The leukemia provide a particularly good example of the relationship between defective (D) and malignancy. Studies of tumor viruses revealed that specific genes [called (D: oncogenes)] are capable of inducing cell transformation. Many viral (D) such as papillomaviral proteins E6 and E7 or adenoviral proteins E1A and E1B inactivate (E: tumor suppressor (proteins)) which regulate cell division and apoptosis in normal cells. The prototype of (E) is (F: Rb / retinoblastoma) – (F) binds to and thus inhibits E2F transcription factors which activate expression of several important genes involved in cell cycle progression in G0 and G1 phase. The second (E) is (G: p53), which is frequently inactivated in a variety of cancer cells. Importantly, loss of (H) prevents DNA damage-induced cell cycle arrest and apoptosis, leading to increased mutation frequencies and a general instability of the cell genome. This genomic instability is a common property of cancer cells and it contribute to further alterations in (D) and (E) during tumor progression. Oncogene의 생성과 작용 Oncogenes in human tumors are derived from genes of normal cells (these genes are called H: proto-oncogenes), products of which functions in signal transduction for cell proliferation in normal cells. Three mechanisms of oncogenesis (a process of the conversion of H to oncogenes) have been identified (I: point mutation): the ras oncogenes differ from their normal counterparts by (I) resulting in single amino acid substitution. These mutant ras gene products remain in the active state thus drive unregulated cell proliferation. (J: translocation or DNA rearragement): the generation of IgH/c-myc in Burkitt’s llymphoma or of Bcr/Abl in chronic myeloid leukemia. Abl protein kinase is fused to an unrelated protein (Bcr) in its N-terminus via the process of (J). The n-terminal half of Abl is important for the regulated functions of Abl protein kinase, thus the Bcr/Abl activates the downstream signaling pathway constitutively resulting in the abnormal and unregulated cell proliferation (K: amplification): some cancer cells contain multicopies of N-myc or erbB-2 genes which induce elevated levels of those gene products. Cancer treatment (L: angiogenesis) is critical for tumor growth. (L) is the formation of new blood vessels to supply the oxygen and nutrients required for repair or regrowth of damaged tissue. Tumor cells are metabolically active and continuously proliferate, thus (L) is the critical step for tumor development and progression. Tumor cells secrete VEGF that stimulate the proliferation of capillary endothelial cells ,resulting in the outgrowth of new capillaries into the tumor. Thus, the inhibition of (L) is a promising new approach to cancer therapy with less side-effects. The development of drugs targeted against specific oncogenes is beginning to lead the discovery of new therapeutic agents that act selectively against cancer cells. Herceptin and Erbitux are (M: monoclonal antibodies 혹은 antibody) against the ErbB-2 and EGFR oncogene proteins (both are protein-tyrosine kinases) respectively. ErbB-2 is overexpressed in about 30% of breast cancers and EGFR is also overexpressed in colorectal cancers. These agents bind to the extracellular domains of the receptors and thus block the downstream signaling pathways, resulting in impaired growth of the cancer cells. Different to Herceptin and Erbitux, Gleevec (STI-571) –a small chemical compound–inhibits (N: protein-tyrosine kinase 혹은 tyrosine kinase) activities of Bcr/Abl, PDGF receptor, Kit oncogenic proteins and it has been proven to be an effective therapy for tumors in which the genes encoding these proteins are mutationally activated oncogenes. It is clear that the rational design of drugs targeted against specific oncogene proteins will play an important role in cancer therapy in the future.