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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 呂勝春(Sheng-Chung Lee) | |
| dc.contributor.author | Ching-Ting Chuang | en |
| dc.contributor.author | 莊淨婷 | zh_TW |
| dc.date.accessioned | 2021-05-20T20:54:59Z | - |
| dc.date.available | 2016-10-05 | |
| dc.date.available | 2021-05-20T20:54:59Z | - |
| dc.date.copyright | 2011-10-05 | |
| dc.date.issued | 2011 | |
| dc.date.submitted | 2011-07-29 | |
| dc.identifier.citation | 1. Katoh, Y., et al., Salt-inducible kinase (SIK) isoforms: their involvement in steroidogenesis and adipogenesis. Mol Cell Endocrinol, 2004. 217(1-2): p. 109-12.
2. Okamoto, M., H. Takemori, and Y. Katoh, Salt-inducible kinase in steroidogenesis and adipogenesis. Trends Endocrinol Metab, 2004. 15(1): p. 21-6. 3. Horike, N., et al., Adipose-specific expression, phosphorylation of Ser794 in insulin receptor substrate-1, and activation in diabetic animals of salt-inducible kinase-2. J Biol Chem, 2003. 278(20): p. 18440-7. 4. Screaton, R.A., et al., The CREB coactivator TORC2 functions as a calcium- and cAMP-sensitive coincidence detector. Cell, 2004. 119(1): p. 61-74. 5. Katoh, Y., et al., Salt-inducible kinase-1 represses cAMP response element-binding protein activity both in the nucleus and in the cytoplasm. Eur J Biochem, 2004. 271(21): p. 4307-19. 6. Du, J., et al., SIK2 can be activated by deprivation of nutrition and it inhibits expression of lipogenic genes in adipocytes. Obesity (Silver Spring), 2008. 16(3): p. 531-8. 7. Kobayashi, T., A. Manno, and A. Kakizuka, Involvement of valosin-containing protein (VCP)/p97 in the formation and clearance of abnormal protein aggregates. Genes Cells, 2007. 12(7): p. 889-901. 8. Kitami, M.I., et al., Dominant-negative effect of mutant valosin-containing protein in aggresome formation. FEBS Lett, 2006. 580(2): p. 474-8. 9. Ju, J.S., et al., Impaired protein aggregate handling and clearance underlie the pathogenesis of p97/VCP-associated disease. J Biol Chem, 2008. 283(44): p. 30289-99. 10. Kim, J., et al., AMPK and mTOR regulate autophagy through direct phosphorylation of Ulk1. Nat Cell Biol, 2011. 13(2): p. 132-41. 11. Egan, D.F., et al., Phosphorylation of ULK1 (hATG1) by AMP-activated protein kinase connects energy sensing to mitophagy. Science, 2011. 331(6016): p. 456-61. 12. Inoki, K., T. Zhu, and K.L. Guan, TSC2 mediates cellular energy response to control cell growth and survival. Cell, 2003. 115(5): p. 577-90. 13. Gwinn, D.M., et al., AMPK phosphorylation of raptor mediates a metabolic checkpoint. Mol Cell, 2008. 30(2): p. 214-26. 14. Ichimura, Y., et al., Structural basis for sorting mechanism of p62 in selective autophagy. J Biol Chem, 2008. 283(33): p. 22847-57. 15. Pankiv, S., et al., p62/SQSTM1 binds directly to Atg8/LC3 to facilitate degradation of ubiquitinated protein aggregates by autophagy. J Biol Chem, 2007. 282(33): p. 24131-45. 16. Bjorkoy, G., et al., p62/SQSTM1 forms protein aggregates degraded by autophagy and has a protective effect on huntingtin-induced cell death. J Cell Biol, 2005. 171(4): p. 603-14. 17. Kuusisto, E., A. Salminen, and I. Alafuzoff, Ubiquitin-binding protein p62 is present in neuronal and glial inclusions in human tauopathies and synucleinopathies. Neuroreport, 2001. 12(10): p. 2085-90. 18. Nagaoka, U., et al., Increased expression of p62 in expanded polyglutamine-expressing cells and its association with polyglutamine inclusions. J Neurochem, 2004. 91(1): p. 57-68. 19. Kabeya, Y., et al., LC3, a mammalian homologue of yeast Apg8p, is localized in autophagosome membranes after processing. EMBO J, 2000. 19(21): p. 5720-8. 20. Seibenhener, M.L., et al., Sequestosome 1/p62 is a polyubiquitin chain binding protein involved in ubiquitin proteasome degradation. Mol Cell Biol, 2004. 24(18): p. 8055-68. 21. Geetha, T. and M.W. Wooten, Structure and functional properties of the ubiquitin binding protein p62. FEBS Lett, 2002. 512(1-3): p. 19-24. 22. Ciani, B., et al., Structure of the ubiquitin-associated domain of p62 (SQSTM1) and implications for mutations that cause Paget's disease of bone. J Biol Chem, 2003. 278(39): p. 37409-12. 23. Kawaguchi, Y., et al., The deacetylase HDAC6 regulates aggresome formation and cell viability in response to misfolded protein stress. Cell, 2003. 115(6): p. 727-38. 24. Iwata, A., et al., HDAC6 and microtubules are required for autophagic degradation of aggregated huntingtin. J Biol Chem, 2005. 280(48): p. 40282-92. 25. Boyault, C., et al., HDAC6-p97/VCP controlled polyubiquitin chain turnover. EMBO J, 2006. 25(14): p. 3357-66. 26. Narita, M., et al., Spatial coupling of mTOR and autophagy augments secretory phenotypes. Science, 2011. 332(6032): p. 966-70. 27. Duran, J.M., et al., Unconventional secretion of Acb1 is mediated by autophagosomes. J Cell Biol, 2010. 188(4): p. 527-36. 28. Nickel, W. and C. Rabouille, Mechanisms of regulated unconventional protein secretion. Nat Rev Mol Cell Biol, 2009. 10(2): p. 148-55. 29. Nickel, W., Pathways of unconventional protein secretion. Curr Opin Biotechnol, 2010. 21(5): p. 621-6. 30. Rivera, V.M., et al., Regulation of protein secretion through controlled aggregation in the endoplasmic reticulum. Science, 2000. 287(5454): p. 826-30. 31. Reed, N.A., et al., Microtubule acetylation promotes kinesin-1 binding and transport. Curr Biol, 2006. 16(21): p. 2166-72. 32. Dompierre, J.P., et al., Histone deacetylase 6 inhibition compensates for the transport deficit in Huntington's disease by increasing tubulin acetylation. J Neurosci, 2007. 27(13): p. 3571-83. 33. Oliver, F.J., et al., Importance of poly(ADP-ribose) polymerase and its cleavage in apoptosis. Lesson from an uncleavable mutant. J Biol Chem, 1998. 273(50): p. 33533-9. 34. Tewari, M., et al., Yama/CPP32 beta, a mammalian homolog of CED-3, is a CrmA-inhibitable protease that cleaves the death substrate poly(ADP-ribose) polymerase. Cell, 1995. 81(5): p. 801-9. | |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/10001 | - |
| dc.description.abstract | 本文主要探討 SIK2 在細胞自噬中扮演的功能。SIK2 為 AMPK 家族的一員，目前已知參與於脂肪細胞的分化和胰島素訊號傳導的調控。SIK2 的其他功能目前尚待研究。先前我們實驗室發現 SIK2 藉由和 p97/VCP 之交互作用而調控 ER-associated protein degradation (ERAD)，也發現 SIK2 可能參與調控蛋白質聚集體的降解。在本篇研究，進一步證實SIK2 可能參與調控細胞自噬。當使用 MG132 來誘導包涵體和聚集體的形成時,發現 SIK2 和 p62 或是 HDAC6 之間有交互作用或複合體之存在。當細胞表現正常激酶活性的 SIK2 時，會導致泛素化蛋白質和 LC3-II 減少，顯示SIK2 極有可能參與處理蛋白質聚集體,且SIK2 可能透過和 p97/VCP 之交互作用並和 p62 、HDAC6 或是 Hsp90複合體之形成達到蛋白質聚集體的降解。另外，在蛋白質分泌的實驗中發現， SIK2 亦可能藉由調控細胞胞器而影響了蛋白質的分泌。本論文之結果顯示: SIK2不但在蛋白質聚集體的降解扮演主要調控功能它也極可能在ERAD和細胞自噬之間扮演協調者之角色。 | zh_TW |
| dc.description.abstract | SIK2 (salt-inducible kinase 2) belongs to members of AMPK family. Other than the regulation of adipocyte differentiation and insulin signal transduction, the functions of SIK2 remain largely unknown. Previously, we showed that SIK2 can interact with p97/VCP to regulate ER-associated protein degradation (ERAD). SIK2 may also involve in inclusion body or aggresome processing. In this study, I investigate how SIK2 is involved in regulation of autophagy. SIK2 could be found in complex containing either p62/SQSTM1 or HDAC6 when the cells are treated with proteosome inhibitor MG132. Overexpression of WT-SIK2 resulted in decrease of ubiquitinated proteins and LC3-II levels. SIK2 may facilitate aggresome processing through p62, HDAC6 or Hsp90. In a ligand-induced protein secretion system using human growth hormone as reporter indicates that SIK2 plays crucial roles in autophagy-mediated protein secretion. My study demonstrated that SIK2 could serve as a positive regulator in autophagic-mediated protein degradation and secretion. Together these results suggest that SIK2 may function as a coordinator for the ER stress response and autophagy. | en |
| dc.description.provenance | Made available in DSpace on 2021-05-20T20:54:59Z (GMT). No. of bitstreams: 1 ntu-100-R96448002-1.pdf: 2864190 bytes, checksum: 66dd98de0e0e2cd55efc872cd635ce17 (MD5) Previous issue date: 2011 | en |
| dc.description.tableofcontents | Master thesis ………..…………………………………………………………. i
中文摘要 ……………..………………………………………………………… ii Abstract ………..………………………………………………………………. iii Contents .…………………….............…………………………………………. iv Introduction ..………………………………………………….……………….. 1 Material and methods ..………………………………………………………… 5 Plasmids, Constructs and Antibodies ……………………………………….. 5 Cell cultures and transfections ………………………………………………. 5 Chemicals treatment ………………………………………………………… 6 Preparation of Whole Cell Extracts …………………………………………. 6 Immunopreciptation assay ………………………………………………...… 6 Flow cytometry ……………………………………………………………… 7 Ligand-induced hGH secretion assay …………………………………..……. 7 Results ..………………………………………………………………………… 8 SIK2 may form complex with p62 and HDAC6 ……………………..…….... 8 SIK2 facilitates the processing of inclusion bodies and aggresomes ……….. 8 Cooperation between SIK2 and HDAC6 facilitates autophagy …………..…. 9 Both kinase activity of SIK2 and chaperone activity of Hsp90 are important for processing of autophagosomes containing SIK2, p97/VCP and Hsp90 ..………………………………………………………… 11 SIK2-regulated vesicle dynamics or autophagy mediates protein secretion from a ligand-induced GH reporter system ……………………………..……….…. 12 SIK2 is important for cell survival when the function of proteosome is impaired ………………………………..……………………. 13 Discussion ..…………………………………………………………………….. 14 References ..………………………………………………..…………………… 18 List of figures ..…………………………………………………………………. 23 Fig. 1 SIK2 may form complex with p62 and HDAC6 ……………………. 23 Fig. 2 p62 and SIK2-containing complex formation appeared to be enhanced both in the soluble and insoluble fractions when cells were treated with MG132. …………………….. 25 Fig. 3 Complex formation between HDAC6 and SIK2 …………………….. 27 Fig. 4 Both kinase activity of SIK2 and chaperone activity of Hsp90 are important for processing of autophagosomes containing SIK2, p97/VCP and Hsp90 ……………………………….. 31 Fig. 5 Autophagy is involved in regulation of ligand-induced protein secretion by SIK2 …………………………………………… 33 Fig. 6 SIK2 is important for the cell survival under stress conditions ……… 35 | |
| dc.language.iso | en | |
| dc.title | SIK2 對細胞自噬的調控 | zh_TW |
| dc.title | Regulation of Autophagy by SIK2 | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 99-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 吳君泰(June-Tai Wu),周祖述(Tzuu-Shuh Jou) | |
| dc.subject.keyword | SIK2,p62,HDAC6,Hsp90,包涵體,蛋白質聚集體, | zh_TW |
| dc.subject.keyword | SIK2,p62,HDAC6,Hsp90,inclusion body,aggresomes, | en |
| dc.relation.page | 36 | |
| dc.rights.note | 同意授權(全球公開) | |
| dc.date.accepted | 2011-08-01 | |
| dc.contributor.author-college | 醫學院 | zh_TW |
| dc.contributor.author-dept | 分子醫學研究所 | zh_TW |
| 顯示於系所單位： | 分子醫學研究所 | |
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