請用此 Handle URI 來引用此文件：
http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/16947完整後設資料紀錄
| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 湯志永(Chih-Yung Tang) | |
| dc.contributor.author | Yi-An Chen | en |
| dc.contributor.author | 陳怡安 | zh_TW |
| dc.date.accessioned | 2021-06-07T23:50:38Z | - |
| dc.date.copyright | 2014-02-25 | |
| dc.date.issued | 2014 | |
| dc.date.submitted | 2014-01-29 | |
| dc.identifier.citation | 參考文獻
Accardi, A., and C. Miller. 2004. Secondary active transport mediated by a prokaryotic homologue of ClC Cl- channels. Nature 427 (6977):803-807. Adrian, R. H., and S. H. Bryant. 1974. On the repetitive discharge in myotonic muscle fibres. J Physiol 240 (2):505-515. Adrian, R. H., and M. W. Marshall. 1976. Action potentials reconstructed in normal and myotonic muscle fibres. J Physiol 258 (1):125-143. Aromataris, E. C., G. Y. Rychkov, B. Bennetts, B. P. Hughes, A. H. Bretag, and M. L. Roberts. 2001. Fast and slow gating of CLC-1: differential effects of 2-(4-chlorophenoxy) propionic acid and dominant negative mutations. Mol Pharmacol 60 (1):200-208. Bauer, C. K., K. Steinmeyer, J. R. Schwarz, and T. J. Jentsch. 1991. Completely functional double-barreled chloride channel expressed from a single Torpedo cDNA. Proc Natl Acad Sci U S A 88 (24):11052-11056. Becker, P. E. 1979. Heterozygote manifestation in recessive generalized myotonia. Hum Genet 46 (3):325-329. Bennetts, B., M. W. Parker, and B. A. Cromer. 2007. Inhibition of skeletal muscle ClC-1 chloride channels by low intracellular pH and ATP. J Biol Chem 282 (45):32780-32791. Bennetts, B., G. Y. Rychkov, H. L. Ng, C. J. Morton, D. Stapleton, M. W. Parker, and B. A. Cromer. 2005. Cytoplasmic ATP-sensing domains regulate gating of skeletal muscle ClC-1 chloride channels. J Biol Chem 280 (37):32452-32458. Bernassola, F., M. Karin, A. Ciechanover, and G. Melino. 2008. The HECT family of E3 ubiquitin ligases: multiple players in cancer development. Cancer Cell 14 (1):10-21. Bretag, A. H. 1987. Muscle chloride channels. Physiol Rev 67 (2):618-724. Bryant, S. H., and A. Morales-Aguilera. 1971. Chloride conductance in normal and myotonic muscle fibres and the action of monocarboxylic aromatic acids. J Physiol 219 (2):367-383. Bykova, E. A., X. D. Zhang, T. Y. Chen, and J. Zheng. 2006. Large movement in the C terminus of CLC-0 chloride channel during slow gating. Nat Struct Mol Biol 13 (12):1115-1119. Cannon, S. C. 2000. Spectrum of sodium channel disturbances in the nondystrophic myotonias and periodic paralyses. Kidney Int 57 (3):772-779. Chang, T. Y., H. C. Kuo, K. M. Hsiao, and C. C. Huang. 2007. Phenotypic variability of autosomal dominant myotonia congenita in a Taiwanese family with muscle chloride channel (CLCN1) mutation. Acta Neurol Taiwan 16 (4):214-220. Chen, L. C., S. Manjeshwar, Y. Lu, D. Moore, B. M. Ljung, W. L. Kuo, S. H. Dairkee, M. Wernick, C. Collins, and H. S. Smith. 1998. The human homologue for the Caenorhabditis elegans cul-4 gene is amplified and overexpressed in primary breast cancers. Cancer Res 58 (16):3677-3683. Chen, T. Y. 2005. Structure and function of clc channels. Annu Rev Physiol 67:809-839. Chen, Z. J., and L. J. Sun. 2009. Nonproteolytic functions of ubiquitin in cell signaling. Mol Cell 33 (3):275-286. Christensen, E. I., O. Devuyst, G. Dom, R. Nielsen, P. Van der Smissen, P. Verroust, M. Leruth, W. B. Guggino, and P. J. Courtoy. 2003. Loss of chloride channel ClC-5 impairs endocytosis by defective trafficking of megalin and cubilin in kidney proximal tubules. Proc Natl Acad Sci U S A 100 (14):8472-8477. Ciechanover, A. 2005. Proteolysis: from the lysosome to ubiquitin and the proteasome. Nat Rev Mol Cell Biol 6 (1):79-87. Ciechanover, A., A. Orian, and A. L. Schwartz. 2000. Ubiquitin-mediated proteolysis: biological regulation via destruction. Bioessays 22 (5):442-451. Colding-Jorgensen, E. 2005. Phenotypic variability in myotonia congenita. Muscle Nerve 32 (1):19-34. Comyn, S. A., G. T. Chan, and T. Mayor. 2013. False start: Cotranslational protein ubiquitination and cytosolic protein quality control. J Proteomics. Cuppoletti, J., K. P. Tewari, A. M. Sherry, E. Y. Kupert, and D. H. Malinowska. 2001. ClC-2 Cl- channels in human lung epithelia: activation by arachidonic acid, amidation, and acid-activated omeprazole. Am J Physiol Cell Physiol 281 (1):C46-54. Deshaies, R. J., and C. A. Joazeiro. 2009. RING domain E3 ubiquitin ligases. Annu Rev Biochem 78:399-434. Devuyst, O., and W. B. Guggino. 2002. Chloride channels in the kidney: lessons learned from knockout animals. Am J Physiol Renal Physiol 283 (6):F1176-1191. Dikic, I., S. Wakatsuki, and K. J. Walters. 2009. Ubiquitin-binding domains - from structures to functions. Nat Rev Mol Cell Biol 10 (10):659-671. Dohna, M., M. Reincke, A. Mincheva, B. Allolio, S. Solinas-Toldo, and P. Lichter. 2000. Adrenocortical carcinoma is characterized by a high frequency of chromosomal gains and high-level amplifications. Genes Chromosomes Cancer 28 (2):145-152. Drummond, D. A., and C. O. Wilke. 2009. The evolutionary consequences of erroneous protein synthesis. Nat Rev Genet 10 (10):715-724. Duan, D., C. Winter, S. Cowley, J. R. Hume, and B. Horowitz. 1997. Molecular identification of a volume-regulated chloride channel. Nature 390 (6658):417-421. Duda, D. M., D. C. Scott, M. F. Calabrese, E. S. Zimmerman, N. Zheng, and B. A. Schulman. 2011. Structural regulation of cullin-RING ubiquitin ligase complexes. Curr Opin Struct Biol 21 (2):257-264. Dulhunty, A. F. 1978. The dependence of membrane potential on extracellular chloride concentration in mammalian skeletal muscle fibres. J Physiol 276:67-82. Dulhunty, A. F. 1979. Distribution of potassium and chloride permeability over the surface and T-tubule membranes of mammalian skeletal muscle. J Membr Biol 45 (3-4):293-310. Dutzler, R. 2007. A structural perspective on ClC channel and transporter function. FEBS Lett 581 (15):2839-2844. Dutzler, R., E. B. Campbell, M. Cadene, B. T. Chait, and R. MacKinnon. 2002. X-ray structure of a ClC chloride channel at 3.0 A reveals the molecular basis of anion selectivity. Nature 415 (6869):287-294. Dutzler, R., E. B. Campbell, and R. MacKinnon. 2003. Gating the selectivity filter in ClC chloride channels. Science 300 (5616):108-112. Emanuele, M. J., A. E. Elia, Q. Xu, C. R. Thoma, L. Izhar, Y. Leng, A. Guo, Y. N. Chen, J. Rush, P. W. Hsu, H. C. Yen, and S. J. Elledge. 2011. Global identification of modular cullin-RING ligase substrates. Cell 147 (2):459-474. Estevez, R., T. Boettger, V. Stein, R. Birkenhager, E. Otto, F. Hildebrandt, and T. J. Jentsch. 2001. Barttin is a Cl- channel beta-subunit crucial for renal Cl- reabsorption and inner ear K+ secretion. Nature 414 (6863):558-561. Estevez, R., M. Pusch, C. Ferrer-Costa, M. Orozco, and T. J. Jentsch. 2004. Functional and structural conservation of CBS domains from CLC chloride channels. J Physiol 557 (Pt 2):363-378. Finley, D. 2009. Recognition and processing of ubiquitin-protein conjugates by the proteasome. Annu Rev Biochem 78:477-513. Fong, P., A. Rehfeldt, and T. J. Jentsch. 1998. Determinants of slow gating in ClC-0, the voltage-gated chloride channel of Torpedo marmorata. Am J Physiol 274 (4 Pt 1):C966-973. Gallaher, J., M. Bier, and J. Siegenbeek van Heukelom. 2009. The role of chloride transport in the control of the membrane potential in skeletal muscle--theory and experiment. Biophys Chem 143 (1-2):18-25. Geiler-Samerotte, K. A., M. F. Dion, B. A. Budnik, S. M. Wang, D. L. Hartl, and D. A. Drummond. 2011. Misfolded proteins impose a dosage-dependent fitness cost and trigger a cytosolic unfolded protein response in yeast. Proc Natl Acad Sci U S A 108 (2):680-685. Goldberg, A. L. 2003. Protein degradation and protection against misfolded or damaged proteins. Nature 426 (6968):895-899. Grunder, S., A. Thiemann, M. Pusch, and T. J. Jentsch. 1992. Regions involved in the opening of CIC-2 chloride channel by voltage and cell volume. Nature 360 (6406):759-762. Hakulinen, E., and J. Thomsen. 1994. [The man behind the syndrome: Julius Thomsen. He himself suffered of a type of myotonia]. Lakartidningen 91 (36):3178-3180. He, Y. J., C. M. McCall, J. Hu, Y. Zeng, and Y. Xiong. 2006. DDB1 functions as a linker to recruit receptor WD40 proteins to CUL4-ROC1 ubiquitin ligases. Genes Dev 20 (21):2949-2954. Higa, L. A., M. Wu, T. Ye, R. Kobayashi, H. Sun, and H. Zhang. 2006. CUL4-DDB1 ubiquitin ligase interacts with multiple WD40-repeat proteins and regulates histone methylation. Nat Cell Biol 8 (11):1277-1283. Higgins, J. J., J. Hao, B. E. Kosofsky, and A. M. Rajadhyaksha. 2008. Dysregulation of large-conductance Ca2+-activated K+ channel expression in nonsyndromal mental retardation due to a cereblon p.R419X mutation. Neurogenetics 9 (3):219-223. Higgins, J. J., J. Pucilowska, R. Q. Lombardi, and J. P. Rooney. 2004. A mutation in a novel ATP-dependent Lon protease gene in a kindred with mild mental retardation. Neurology 63 (10):1927-1931. Hofmann, R. M., and C. M. Pickart. 1999. Noncanonical MMS2-encoded ubiquitin-conjugating enzyme functions in assembly of novel polyubiquitin chains for DNA repair. Cell 96 (5):645-653. Hohberger, B., and R. Enz. 2009. Cereblon is expressed in the retina and binds to voltage-gated chloride channels. FEBS Lett 583 (4):633-637. Hwang, W. W., S. Venkatasubrahmanyam, A. G. Ianculescu, A. Tong, C. Boone, and H. D. Madhani. 2003. A conserved RING finger protein required for histone H2B monoubiquitination and cell size control. Mol Cell 11 (1):261-266. Iovine, B., M. L. Iannella, and M. A. Bevilacqua. 2011. Damage-specific DNA binding protein 1 (DDB1): a protein with a wide range of functions. Int J Biochem Cell Biol 43 (12):1664-1667. Isidor, B., O. Pichon, S. Baron, A. David, and C. Le Caignec. 2010. Deletion of the CUL4B gene in a boy with mental retardation, minor facial anomalies, short stature, hypogonadism, and ataxia. Am J Med Genet A 152A (1):175-180. Ito, T., H. Ando, T. Suzuki, T. Ogura, K. Hotta, Y. Imamura, Y. Yamaguchi, and H. Handa. 2010. Identification of a primary target of thalidomide teratogenicity. Science 327 (5971):1345-1350. Jackson, S., and Y. Xiong. 2009. CRL4s: the CUL4-RING E3 ubiquitin ligases. Trends Biochem Sci 34 (11):562-570. Jentsch, T. J., T. Maritzen, and A. A. Zdebik. 2005. Chloride channel diseases resulting from impaired transepithelial transport or vesicular function. J Clin Invest 115 (8):2039-2046. Jentsch, T. J., V. Stein, F. Weinreich, and A. A. Zdebik. 2002. Molecular structure and physiological function of chloride channels. Physiol Rev 82 (2):503-568. Jentsch, T. J., K. Steinmeyer, and G. Schwarz. 1990. Primary structure of Torpedo marmorata chloride channel isolated by expression cloning in Xenopus oocytes. Nature 348 (6301):510-514. Jo, S., K. H. Lee, S. Song, Y. K. Jung, and C. S. Park. 2005. Identification and functional characterization of cereblon as a binding protein for large-conductance calcium-activated potassium channel in rat brain. J Neurochem 94 (5):1212-1224. Johnson, E. S., P. C. Ma, I. M. Ota, and A. Varshavsky. 1995. A proteolytic pathway that recognizes ubiquitin as a degradation signal. J Biol Chem 270 (29):17442-17456. Kamsteeg, E. J., G. Hendriks, M. Boone, I. B. Konings, V. Oorschot, P. van der Sluijs, J. Klumperman, and P. M. Deen. 2006. Short-chain ubiquitination mediates the regulated endocytosis of the aquaporin-2 water channel. Proc Natl Acad Sci U S A 103 (48):18344-18349. Kasper, D., R. Planells-Cases, J. C. Fuhrmann, O. Scheel, O. Zeitz, K. Ruether, A. Schmitt, M. Poet, R. Steinfeld, M. Schweizer, U. Kornak, and T. J. Jentsch. 2005. Loss of the chloride channel ClC-7 leads to lysosomal storage disease and neurodegeneration. EMBO J 24 (5):1079-1091. Kawasaki, M., S. Uchida, T. Monkawa, A. Miyawaki, K. Mikoshiba, F. Marumo, and S. Sasaki. 1994. Cloning and expression of a protein kinase C-regulated chloride channel abundantly expressed in rat brain neuronal cells. Neuron 12 (3):597-604. Kee, Y., and J. M. Huibregtse. 2007. Regulation of catalytic activities of HECT ubiquitin ligases. Biochem Biophys Res Commun 354 (2):329-333. Komander, D. 2009. The emerging complexity of protein ubiquitination. Biochem Soc Trans 37 (Pt 5):937-953. Kornak, U., D. Kasper, M. R. Bosl, E. Kaiser, M. Schweizer, A. Schulz, W. Friedrich, G. Delling, and T. J. Jentsch. 2001. Loss of the ClC-7 chloride channel leads to osteopetrosis in mice and man. Cell 104 (2):205-215. Kronke, J., N. D. Udeshi, A. Narla, P. Grauman, S. N. Hurst, M. McConkey, T. Svinkina, D. Heckl, E. Comer, X. Li, C. Ciarlo, E. Hartman, N. Munshi, M. Schenone, S. L. Schreiber, S. A. Carr, and B. L. Ebert. 2013. Lenalidomide Causes Selective Degradation of IKZF1 and IKZF3 in Multiple Myeloma Cells. Science. Lange, P. F., L. Wartosch, T. J. Jentsch, and J. C. Fuhrmann. 2006. ClC-7 requires Ostm1 as a beta-subunit to support bone resorption and lysosomal function. Nature 440 (7081):220-223. Lee, J., and P. Zhou. 2007. DCAFs, the missing link of the CUL4-DDB1 ubiquitin ligase. Mol Cell 26 (6):775-780. Lee, J., and P. Zhou. 2012. Pathogenic Role of the CRL4 Ubiquitin Ligase in Human Disease. Front Oncol 2:21. Lee, T. T., X. D. Zhang, C. C. Chuang, J. J. Chen, Y. A. Chen, S. C. Chen, T. Y. Chen, and C. Y. Tang. 2013. Myotonia congenita mutation enhances the degradation of human CLC-1 chloride channels. PLoS One 8 (2):e55930. Li, T., X. Chen, K. C. Garbutt, P. Zhou, and N. Zheng. 2006. Structure of DDB1 in complex with a paramyxovirus V protein: viral hijack of a propeller cluster in ubiquitin ligase. Cell 124 (1):105-117. Li, X., T. Wang, Z. Zhao, and S. A. Weinman. 2002. The ClC-3 chloride channel promotes acidification of lysosomes in CHO-K1 and Huh-7 cells. Am J Physiol Cell Physiol 282 (6):C1483-1491. Lloyd, S. E., S. H. Pearce, S. E. Fisher, K. Steinmeyer, B. Schwappach, S. J. Scheinman, B. Harding, A. Bolino, M. Devoto, P. Goodyer, S. P. Rigden, O. Wrong, T. J. Jentsch, I. W. Craig, and R. V. Thakker. 1996. A common molecular basis for three inherited kidney stone diseases. Nature 379 (6564):445-449. Luzio, J. P., B. M. Mullock, P. R. Pryor, M. R. Lindsay, D. E. James, and R. C. Piper. 2001. Relationship between endosomes and lysosomes. Biochem Soc Trans 29 (Pt 4):476-480. MacGurn, J. A., P. C. Hsu, and S. D. Emr. 2012. Ubiquitin and membrane protein turnover: from cradle to grave. Annu Rev Biochem 81:231-259. Middleton, R. E., D. J. Pheasant, and C. Miller. 1996. Homodimeric architecture of a ClC-type chloride ion channel. Nature 383 (6598):337-340. Milhollen, M. A., T. Traore, J. Adams-Duffy, M. P. Thomas, A. J. Berger, L. Dang, L. R. Dick, J. J. Garnsey, E. Koenig, S. P. Langston, M. Manfredi, U. Narayanan, M. Rolfe, L. M. Staudt, T. A. Soucy, J. Yu, J. Zhang, J. B. Bolen, and P. G. Smith. 2010. MLN4924, a NEDD8-activating enzyme inhibitor, is active in diffuse large B-cell lymphoma models: rationale for treatment of NF-{kappa}B-dependent lymphoma. Blood 116 (9):1515-1523. Miller, C. 1982. Open-state substructure of single chloride channels from Torpedo electroplax. Philos Trans R Soc Lond B Biol Sci 299 (1097):401-411. Mohammad-Panah, R., R. Harrison, S. Dhani, C. Ackerley, L. J. Huan, Y. Wang, and C. E. Bear. 2003. The chloride channel ClC-4 contributes to endosomal acidification and trafficking. J Biol Chem 278 (31):29267-29277. Morris, J. R., and E. Solomon. 2004. BRCA1 : BARD1 induces the formation of conjugated ubiquitin structures, dependent on K6 of ubiquitin, in cells during DNA replication and repair. Hum Mol Genet 13 (8):807-817. Nilius, B., and G. Droogmans. 2003. Amazing chloride channels: an overview. Acta Physiol Scand 177 (2):119-147. Ohtake, F., A. Baba, I. Takada, M. Okada, K. Iwasaki, H. Miki, S. Takahashi, A. Kouzmenko, K. Nohara, T. Chiba, Y. Fujii-Kuriyama, and S. Kato. 2007. Dioxin receptor is a ligand-dependent E3 ubiquitin ligase. Nature 446 (7135):562-566. Petroski, M. D., and R. J. Deshaies. 2005. Function and regulation of cullin-RING ubiquitin ligases. Nat Rev Mol Cell Biol 6 (1):9-20. Picollo, A., and M. Pusch. 2005. Chloride/proton antiporter activity of mammalian CLC proteins ClC-4 and ClC-5. Nature 436 (7049):420-423. Piwon, N., W. Gunther, M. Schwake, M. R. Bosl, and T. J. Jentsch. 2000. ClC-5 Cl- -channel disruption impairs endocytosis in a mouse model for Dent's disease. Nature 408 (6810):369-373. Plans, V., G. Rickheit, and T. J. Jentsch. 2009. Physiological roles of CLC Cl(-)/H (+) exchangers in renal proximal tubules. Pflugers Arch 458 (1):23-37. Poet, M., U. Kornak, M. Schweizer, A. A. Zdebik, O. Scheel, S. Hoelter, W. Wurst, A. Schmitt, J. C. Fuhrmann, R. Planells-Cases, S. E. Mole, C. A. Hubner, and T. J. Jentsch. 2006. Lysosomal storage disease upon disruption of the neuronal chloride transport protein ClC-6. Proc Natl Acad Sci U S A 103 (37):13854-13859. Pusch, M. 2002. Myotonia caused by mutations in the muscle chloride channel gene CLCN1. Hum Mutat 19 (4):423-434. Pusch, M., K. Steinmeyer, and T. J. Jentsch. 1994. Low single channel conductance of the major skeletal muscle chloride channel, ClC-1. Biophys J 66 (1):149-152. Richardson, P. G., B. Barlogie, J. Berenson, S. Singhal, S. Jagannath, D. Irwin, S. V. Rajkumar, G. Srkalovic, M. Alsina, R. Alexanian, D. Siegel, R. Z. Orlowski, D. Kuter, S. A. Limentani, S. Lee, T. Hideshima, D. L. Esseltine, M. Kauffman, J. Adams, D. P. Schenkein, and K. C. Anderson. 2003. A phase 2 study of bortezomib in relapsed, refractory myeloma. N Engl J Med 348 (26):2609-2617. Russell, J. M. 2000. Sodium-potassium-chloride cotransport. Physiol Rev 80 (1):211-276. Rychkov, G. Y., M. Pusch, D. S. Astill, M. L. Roberts, T. J. Jentsch, and A. H. Bretag. 1996. Concentration and pH dependence of skeletal muscle chloride channel ClC-1. J Physiol 497 ( Pt 2):423-435. Rychkov, G. Y., M. Pusch, M. L. Roberts, T. J. Jentsch, and A. H. Bretag. 1998. Permeation and block of the skeletal muscle chloride channel, ClC-1, by foreign anions. J Gen Physiol 111 (5):653-665. Sarikas, A., T. Hartmann, and Z. Q. Pan. 2011. The cullin protein family. Genome Biol 12 (4):220. Saviane, C., F. Conti, and M. Pusch. 1999. The muscle chloride channel ClC-1 has a double-barreled appearance that is differentially affected in dominant and recessive myotonia. J Gen Physiol 113 (3):457-468. Scheel, O., A. A. Zdebik, S. Lourdel, and T. J. Jentsch. 2005. Voltage-dependent electrogenic chloride/proton exchange by endosomal CLC proteins. Nature 436 (7049):424-427. Skaar, J. R., L. Florens, T. Tsutsumi, T. Arai, A. Tron, S. K. Swanson, M. P. Washburn, and J. A. DeCaprio. 2007. PARC and CUL7 form atypical cullin RING ligase complexes. Cancer Res 67 (5):2006-2014. Soucy, T. A., P. G. Smith, M. A. Milhollen, A. J. Berger, J. M. Gavin, S. Adhikari, J. E. Brownell, K. E. Burke, D. P. Cardin, S. Critchley, C. A. Cullis, A. Doucette, J. J. Garnsey, J. L. Gaulin, R. E. Gershman, A. R. Lublinsky, A. McDonald, H. Mizutani, U. Narayanan, E. J. Olhava, S. Peluso, M. Rezaei, M. D. Sintchak, T. Talreja, M. P. Thomas, T. Traore, S. Vyskocil, G. S. Weatherhead, J. Yu, J. Zhang, L. R. Dick, C. F. Claiborne, M. Rolfe, J. B. Bolen, and S. P. Langston. 2009. An inhibitor of NEDD8-activating enzyme as a new approach to treat cancer. Nature 458 (7239):732-736. Steinmeyer, K., C. Lorenz, M. Pusch, M. C. Koch, and T. J. Jentsch. 1994. Multimeric structure of ClC-1 chloride channel revealed by mutations in dominant myotonia congenita (Thomsen). EMBO J 13 (4):737-743. Steinmeyer, K., C. Ortland, and T. J. Jentsch. 1991. Primary structure and functional expression of a developmentally regulated skeletal muscle chloride channel. Nature 354 (6351):301-304. Steinmeyer, K., B. Schwappach, M. Bens, A. Vandewalle, and T. J. Jentsch. 1995. Cloning and functional expression of rat CLC-5, a chloride channel related to kidney disease. J Biol Chem 270 (52):31172-31177. Stobrawa, S. M., T. Breiderhoff, S. Takamori, D. Engel, M. Schweizer, A. A. Zdebik, M. R. Bosl, K. Ruether, H. Jahn, A. Draguhn, R. Jahn, and T. J. Jentsch. 2001. Disruption of ClC-3, a chloride channel expressed on synaptic vesicles, leads to a loss of the hippocampus. Neuron 29 (1):185-196. Strange, K. 2002. Of mice and worms: novel insights into ClC-2 anion channel physiology. News Physiol Sci 17:11-16. Suzuki, T., T. Rai, A. Hayama, E. Sohara, S. Suda, T. Itoh, S. Sasaki, and S. Uchida. 2006. Intracellular localization of ClC chloride channels and their ability to form hetero-oligomers. J Cell Physiol 206 (3):792-798. Tang, C. Y., and T. Y. Chen. 2011. Physiology and pathophysiology of CLC-1: mechanisms of a chloride channel disease, myotonia. J Biomed Biotechnol 2011:685328. Tarpey, P. S., F. L. Raymond, S. O'Meara, S. Edkins, J. Teague, A. Butler, E. Dicks, C. Stevens, C. Tofts, T. Avis, S. Barthorpe, G. Buck, J. Cole, K. Gray, K. Halliday, R. Harrison, K. Hills, A. Jenkinson, D. Jones, A. Menzies, T. Mironenko, J. Perry, K. Raine, D. Richardson, R. Shepherd, A. Small, J. Varian, S. West, S. Widaa, U. Mallya, J. Moon, Y. Luo, S. Holder, S. F. Smithson, J. A. Hurst, J. Clayton-Smith, B. Kerr, J. Boyle, M. Shaw, L. Vandeleur, J. Rodriguez, R. Slaugh, D. F. Easton, R. Wooster, M. Bobrow, A. K. Srivastava, R. E. Stevenson, C. E. Schwartz, G. Turner, J. Gecz, P. A. Futreal, M. R. Stratton, and M. Partington. 2007. Mutations in CUL4B, which encodes a ubiquitin E3 ligase subunit, cause an X-linked mental retardation syndrome associated with aggressive outbursts, seizures, relative macrocephaly, central obesity, hypogonadism, pes cavus, and tremor. Am J Hum Genet 80 (2):345-352. Thiemann, A., S. Grunder, M. Pusch, and T. J. Jentsch. 1992. A chloride channel widely expressed in epithelial and non-epithelial cells. Nature 356 (6364):57-60. Thrower, J. S., L. Hoffman, M. Rechsteiner, and C. M. Pickart. 2000. Recognition of the polyubiquitin proteolytic signal. EMBO J 19 (1):94-102. Tseng, P. Y., B. Bennetts, and T. Y. Chen. 2007. Cytoplasmic ATP inhibition of CLC-1 is enhanced by low pH. J Gen Physiol 130 (2):217-221. Tseng, P. Y., W. P. Yu, H. Y. Liu, X. D. Zhang, X. Zou, and T. Y. Chen. 2011. Binding of ATP to the CBS domains in the C-terminal region of CLC-1. J Gen Physiol 137 (4):357-368. Wente, M. N., G. Eibl, H. A. Reber, H. Friess, M. W. Buchler, and O. J. Hines. 2005. The proteasome inhibitor MG132 induces apoptosis in human pancreatic cancer cells. Oncol Rep 14 (6):1635-1638. Xin, W., N. Xiaohua, C. Peilin, C. Xin, S. Yaqiong, and W. Qihan. 2008. Primary function analysis of human mental retardation related gene CRBN. Mol Biol Rep 35 (2):251-256. Xu, P., D. M. Duong, N. T. Seyfried, D. Cheng, Y. Xie, J. Robert, J. Rush, M. Hochstrasser, D. Finley, and J. Peng. 2009. Quantitative proteomics reveals the function of unconventional ubiquitin chains in proteasomal degradation. Cell 137 (1):133-145. Yang, H. H., R. Vescio, D. Schenkein, and J. R. Berenson. 2003. A prospective, open-label safety and efficacy study of combination treatment with bortezomib (PS-341, velcade and melphalan in patients with relapsed or refractory multiple myeloma. Clin Lymphoma 4 (2):119-122. Yasui, K., S. Arii, C. Zhao, I. Imoto, M. Ueda, H. Nagai, M. Emi, and J. Inazawa. 2002. TFDP1, CUL4A, and CDC16 identified as targets for amplification at 13q34 in hepatocellular carcinomas. Hepatology 35 (6):1476-1484. Ye, Y., and M. Rape. 2009. Building ubiquitin chains: E2 enzymes at work. Nat Rev Mol Cell Biol 10 (11):755-764. Zifarelli, G., and M. Pusch. 2007. CLC chloride channels and transporters: a biophysical and physiological perspective. Rev Physiol Biochem Pharmacol 158:23-76. Zifarelli, G., and M. Pusch. 2009. Intracellular regulation of human ClC-5 by adenine nucleotides. EMBO Rep 10 (10):1111-1116. Zimmerman, E. S., B. A. Schulman, and N. Zheng. 2010. Structural assembly of cullin-RING ubiquitin ligase complexes. Curr Opin Struct Biol 20 (6):714-721. | |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/16947 | - |
| dc.description.abstract | 先天性肌肉強直症 (myotonia congenita) 是一種影響骨骼肌舒張的神經肌肉遺傳疾病，這是由於負責轉錄骨骼肌上人類第一型氯離子通道的CLCN1基因突變所造成的結果。人類第一型氯離子通道 (human CLC-1 Chloride channels, CLC-1) ，其功能主要為調節骨骼肌細胞膜的興奮性。先前研究已知，先天性肌肉強直症之相關突變會改變CLC-1的電位依賴性進而影響離子通道的門閥開關比例；此外，某些相關突變也會影響CLC-1表現總量與分布型態。近來亦有研究指出，先天性肌肉強直症相關突變會促進CLC-1之降解 (degradation)，但現今對於CLC-1之降解調控途徑及機制尚未釐清。本篇論文旨在利用正常型以及突變型A531V探討CLC-1之降解途徑。
我們的主要目標是要找出負責CLC-1降解之E3連接酶 (E3 ligase)。首先，我們利用MLN4924藥物處理辨別出CLC-1之E3連接酶屬於cullin-RING ubiquitin ligases (CRLs)次家族。為了進一步找出參與CLC-1泛素化作用之E3連接酶，我們選用了具有dominant negative (DN)效果的cullin (CUL)構築質體，利用西方墨點法分析比較共同轉染 (co-expression)後CLC-1之蛋白質表現量的差異，發現CUL4A與CUL4B組別中CLC-1之表現量顯著增加。我們也以泛素化標定 (ubiquitination)實驗觀察到DN-CUL4A組別明顯減少了CLC-1被泛素化的程度。而後我們利用共同免疫沉澱法 (Co-IP)發現CLC-1會與CUL4A之adaptor蛋白DDB1以及CUL4A之substrate receptor蛋白cereblon (CRBN)共同存在相同的protein complex。此外，DN-CRBN也會造成CLC-1蛋白總量的增加，並使CLC-1之泛素作用程度減少。我們還證明DN-CUL4A與DN-CRBN皆可延長CLC-1之蛋白質代謝半衰期。細胞表面生物素標定 (surface biotinylation)的實驗結果顯示在與DN-CUL4A共同轉染的情況下，CLC-1蛋白質運送至細胞膜效率並不會有明顯的改變。當我們以肌強直相關突變型A531V重複以上之實驗結果發現其蛋白質總量之增加、泛素化作程度之下降以及蛋白質代謝半衰期之延長的效果都比正常型的反應更為明顯，代表A531V突變型CLC-1蛋白質確實是受到顯著的降解調控機制。由以上實驗結果我們證明了調控CLC-1的E3連接酶應當為CUL4-DDB1-CRBN所組成的多單元複合體。 為了進一步探討CLC-1泛素化之鍵結方式，我們發現利用泛素 (Ubiquitin, Ub)所有位置之離胺酸 (K)皆定點突變為精胺酸 (R)而只能形成單一泛素化作用的構築質體 (Ub-K0)可以使CLC-1蛋白總量明顯增加。而泛素不同位置之離胺酸定點突變為精胺酸的構築質體雖然在正常型CLC-1組別不具有顯著差異，但是Ub-K6R以及Ub-K48R可以使A531V CLC-1蛋白質表現總量增加。綜合以上結果，我們推測CLC-1是以聚泛素鏈形式進行降解機制之標定，並且其聚泛素鏈是由泛素K48位置鍵結所形成。 | zh_TW |
| dc.description.abstract | Myotonia congenita, a hereditary neuromuscular disorder that disrupts skeletal muscle relaxation, is caused by mutations in the human CLCN1 gene on chromosome 7. The function of human CLC-1 chloride channels (CLC-1) is to regulate the membrane excitability of skeletal muscles. Myotonia congenita-related mutations are known to alter the voltage dependence and open probability of CLC-1 channels, as well as the biogenesis and the subcellular distribution of the Cl- channel. Recent evidence further indicates that myotonia congenita mutation may enhance the degradation of CLC-1 channels. In this thesis, we aim to decipher the proteasomal degradation mechanism of CLC-1 channels by studying the wild type (WT) and the mutant A531V.
The substrate specificity of the ubiquitin-conjugation system is mainly mediated by E3 ligases. By treating with MLN4924, we examine the E3 ligase of CLC-1 belongs to CRLs. To find E3 ligases of CLC-1, we choose CUL constructs that has dominant-negative effects to co-express with CLC-1. We find that DN-CUL4A and DN-CUL4B increase the total protein expression level of CLC-1. DN-CUL4A also reduced the ubiquitination level of CLC-1. We further find the adaptor, DDB1, and the substrate receptor, CRBN, of CRL4s by using co-immunoprecipitation. Furthermore, we find that DN-CRBN could increase the total protein expression level of CLC-1 as well as reduce the ubiquitination level of CLC-1by, prolong the protein half-life via cycloheximide treatment. Moreover, we discover that co-expression CLC-1 with DN-CUL4A or DN-CUL4B can enhance CLC-1 protein trafficking to cell membrane by biotinylation technique. We also proved that the mutation related to myotonia congenita, A531V, has more significant effect to DN-RING domain E3 ligase comparing to wild type CLC-1. These results are consistent with the mutant type were more significant than wild-type. In addition, in order to understand how ubiquitin is covalently linked to CLC-1 protein via specific residues, can use different sites of lysine to form different types of ubiquitin chain, co-expressed CLC-1 WT and A531V proteins with various ubiquitin constructs harboring different lysine mutations. In this result, we find that ubiquitin covalently linked to CLC-1 by using K48 residues, which would be recognized by proteasome. | en |
| dc.description.provenance | Made available in DSpace on 2021-06-07T23:50:38Z (GMT). No. of bitstreams: 1 ntu-103-R00441010-1.pdf: 5194315 bytes, checksum: 7022a69fb3a5a43d78c8e39b4a803b5f (MD5) Previous issue date: 2014 | en |
| dc.description.tableofcontents | 目錄
中文摘要 i Abstract iii 目錄 v 圖目錄 viii 附圖目錄 x 第一章 導論 1 1.1 Chloride channel 1 1.2 The CLC Family 1 1.3 CLC-1 3 1.4 Myotonia congenita 5 1.5 Overview of myotonia congenita-related CLC-1 mutations 5 1.6 Protein degradation 7 1.7 Ubiquitin/Proteasome System 7 1.8 E3 Ubiquitin Ligase 9 1.9 Aim of the study 10 第二章 材料與方法 11 2.1 質體 (Plasmid) 11 2.2 PCR mutagenesis 12 2.3 HEK293T細胞培養 (Cell culture) 13 2.4 磷酸鈣轉染 (CaPh transfection) 14 2.5 脂質體2000轉染 (Lipofectamine 2000 transfection) 15 2.6 細胞溶解與蛋白質樣品製備 (Cell lysis and preparation of protein samples) 15 2.7 MLN4924細胞處理 15 2.8 共同免疫沉澱 (Co-immunoprecipitation) 16 2.9 泛素化修飾 (Ubiqutination) 16 2.10 細胞表面生物素標定 (Biotinylation) 17 2.11 CHX細胞處理 (Cycloheximide treatment) 17 2.12 慢病毒感染 (Lentivirus infection) 18 2.13 骨骼肌細胞萃取 (Skeletal muscle extraction) 18 2.14 西方墨點法 (Western blot) 18 2.15 資料統計與分析 20 第三章 結果 21 3.1 MLN4924 使CLC-1蛋白質表現量增加 21 3.2 CUL4參與CLC-1之泛素化作用 21 3.3 DDB1與CLC-1有交互作用 22 3.4 CLC-1的substrate receptor並非DDB2 23 3.5 CRBN與CLC-1有交互作用 23 3.6 CRBN參與CLC-1之泛素化作用 24 3.7 DN-CUL4A與DN-CRBN影響CLC-1代謝半衰期 25 3.8 DN-CUL4A使CLC-1在細胞膜上表現量增加 26 3.9 剔除 CUL4使CLC-1表現量增加 27 3.10 確認骨骼肌中CLC-1與CRBN表現 27 3.11 CLC-1聚泛素鏈之鍵結形式 27 第四章 討論 29 4.1 CRL4A與CRL4B參與CLC-1之蛋白酶體降解途徑 29 4.2 CRBN扮演CLC-1蛋白酶體降解途徑之substrate receptor 32 4.3 CLC-1聚泛素鏈之鍵結形式 33 4.4 CLC-1之降解途徑與先天性肌強直症之致病機轉 34 4.5 待釐清之問題以及後續的實驗設計 35 結論 37 圖表 38 附圖 65 參考文獻 70 | |
| dc.language.iso | zh-TW | |
| dc.subject | 蛋白?體降解 | zh_TW |
| dc.subject | 人類第一型氯離子通道 | zh_TW |
| dc.subject | E3連接? | zh_TW |
| dc.subject | proteasomal degradation | en |
| dc.subject | CLC-1 | en |
| dc.subject | E3 ligase | en |
| dc.title | 人類第一型氯離子通道之蛋白酶體降解途徑 | zh_TW |
| dc.title | The Proteasomal Degradation Pathway of Human CLC-1 Chloride Channels | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 102-1 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 鄭瓊娟(Jiuan-Jeng Chung),胡孟君,吳君泰(June-Tai Wu) | |
| dc.subject.keyword | 人類第一型氯離子通道,E3連接?,蛋白?體降解, | zh_TW |
| dc.subject.keyword | CLC-1,E3 ligase,proteasomal degradation, | en |
| dc.relation.page | 80 | |
| dc.rights.note | 未授權 | |
| dc.date.accepted | 2014-01-29 | |
| dc.contributor.author-college | 醫學院 | zh_TW |
| dc.contributor.author-dept | 生理學研究所 | zh_TW |
| 顯示於系所單位： | 生理學科所 | |
文件中的檔案：
| 檔案 | 大小 | 格式 | |
|---|---|---|---|
| ntu-103-1.pdf 未授權公開取用 | 5.07 MB | Adobe PDF |
系統中的文件，除了特別指名其著作權條款之外，均受到著作權保護，並且保留所有的權利。