4bTheNobelPrizeinChe mistry2004

Information about 4bTheNobelPrizeinChe mistry2004

Published on October 15, 2007

Author: Abhil

Source: authorstream.com

Content

The Nobel Prize in Chemistry 2004:  The Nobel Prize in Chemistry 2004 96羅致宏 88鄭為遠 62陳昭佑 61陳建鴻 79劉郁軒 76楊曜鴻 名詞解釋:  名詞解釋 History&Backgroud of Ubiquitin!!:  History&Backgroud of Ubiquitin!! Slide6:  Aaron Ciechanover Birth:1947, Haifa, Israel 醫學博士 任教於以色列工學院 Avram Hershko 1937出生 任教於以色列工學院,與Aaron Ciechanover共事 Irwin Rose :  Irwin Rose 1926 目前在加州大學擔任教授 Background:  Background 蛋白質分解需要能量嗎? Trypsin&Lysosome 1950年,實驗發現蛋白質分解需要能量 History:  History 1975 Ubiquitin was first isolated from the thymus 1977 Goldberg 做了一個實驗 1978 Discovery of APF-1(ATP-dependent proteolysis factor 1) 1981~1983 Hershko&Ciechanover& Rose 分離出E1,E2和E3 Discovery of APF-1:  Discovery of APF-1 從網狀紅血球萃取 A small heat-stable polypeptide Divided by chromatography 為什麼需要UBQUITIN?:  為什麼需要UBQUITIN? 30%製造的蛋白質都會被分解 提高分解效率 Introduction:  Introduction What’s Ubiquitin?:  What’s Ubiquitin? Main role: become a “label” to target the substrate protein 死亡之吻 Protein degradation 蛋白質降解 Apoptosis: programmed cell death 最早命名為APF-1(ATP-dependent proteolysis factor 1) 結構:  結構 1977 Harris Goldknopf and Ira Busch DNA-associated 76 a.a 一個C端兩個N端 C端具有gly可與 protein substrate (最早在histone H2A)中 的lys形成類肽鍵 Slide17:  E1:Ub-activating enzyme(需耗ATP) E2:Ub-conjugating enzyme E3:Ub-ligase Ubiquination的放大:  Ubiquination的放大 兩種E3 Ubiquitin ligases:  兩種E3 Ubiquitin ligases HECT-domain proteins 先與Ub形成 thiol-ester bond 在其轉移到protein substrate前 RING finger proteins 帶領E2-ubiquitin complex至protein substrate E3是種complex RING finger protein:  RING finger protein 一致的序列 8個Cys與His與Zn ion形成cross-braced fashion 有些獨立作用如Ubr1/E3α其他在complex中如SCF complex PROTEASOME:  PROTEASOME A human cell contains about 30,000 proteasomes Barrel froemed Degrade proteins to 7~9a.a. polypeptides Active surface- inside The only way in to the active surface is via the "lock" The peptides formed are released from the other end of the proteasome. Proteasome cannot choose proteins, but E3 do it! proteasome:  proteasome 蛋白酶體 for endogenous proteins (細胞內自我合成的)lysosome for extracellular proteins from endocytosis 可用來對抗improperly folded proteins Slide26:  Alfred Goldberg (Harvard Med) & Martin Rechsteiner (Utah) in 1980's 90% of all abnormal, misfolded proteins Transcription factors 蛋白質的辨識”N-end rule”:  蛋白質的辨識”N-end rule” 在Protein substrate的N端有一特定,destabilizing的aa residue(來自post-translational modification) N-Degrons N端destabilizing residue Internal Lys (site for Ub attachment) Slide29:  3 type of substrate Type I substrates are proteins that have a basic NH2-terminal residue (Arg, His, Lys) Type II substrates are proteins with bulky-hydrophobic N-termini (Leu, Trp, Phe, and Tyr) Type III substrates have Ser, Ala, and Thr residue E3α E3β Ubiquitin並非唯一的tag:  Ubiquitin並非唯一的tag Slide31:  Ubiquitin 與 cell cycle 之關聯 Cell cycle:  Cell cycle Ubiquitin-mediated proteolysis 控制了細胞週期中多數的細胞調節蛋白 細胞週期為單一方向不可逆 Ub在各階段便有著解鎖的功能,使得細胞得以進入下一週期 如何將substrate標記?:  如何將substrate標記? Ub系統常會以single subunits 或 multiprotein complexes 來擔任需 Ubiquitinated的substrate的辨識因子 在此以較龐大的Ubiquitin ligases中的 SCF complexes為例子 SCF complexes:  SCF complexes SCF complexes:  SCF complexes 其中S 為 Skp1 ;C 為 Cul1 ;F 為 F-box protein 而FBP的組成直接影響了Substrate recognition FBP之組成:  FBP之組成 FBP 基本是以40個a.a 的box(又稱為F-box)再以WD-40 或 leucine-rich repeats 等方式以增加其多樣性 結果:得以讓SCF Complexe 能夠Ubiquitinate 多種不同的substrate SCF 控制 cell cycle 之機制:  SCF 控制 cell cycle 之機制 當兩種CDK inhibitors p21 及 p27 存在時,細胞會無法由 G1轉往 S 期 此時便需要 SCFSkp2 來Ub化p21 及 p27 Slide38:  Skp2 和 Cks1 同為不穩定的蛋白質,如果沒預先被分解,細胞就會提早進入S期 APC/C (anaphase-promoting complex/cyclosome) 即為調節Skp2 和 Cks1的另一個Ub ligase Slide39:  簡而言之:整個cell cycle是由多種Ub ligase所交互作用而成 ex : APC/C 和 SCF FBP ß-Trcp1 負責 Emi1(APC/C的抑制物的)的分解 Inactivation of the ß-Trcp1 造成老鼠胚胎纖維組織母細胞 Lengthened mitosis Centrosome overduplication Multipolar metaphase spindles Misaligned chromosomes Slide40:  在許多人類癌症細胞中發現造成低含量的p27不是因為p27 gene的表現改變,而是過多不正常的Ub化的水解!! 造成細胞不正常增生 Carcinomas!! Low expression of p27 Ubiquitin and Diseases :  Ubiquitin and Diseases Slide42:  What can go wrong in the UPS (Ubiquitin Proteasome System) to cause disorder and/or disease? Human papilloma virus (HPV):  Human papilloma virus (HPV) What is HPV? Human papilloma virus (HPV):  Human papilloma virus (HPV) What’s the relationship between HPV and Ub? Huntinton’s disease(HD):  Huntinton’s disease(HD) 造成亨丁頓舞蹈症的基因是在第四對體染色體,與性別無關。 CAG序列重複次數較常人多 症狀 UB & HD:  UB & HD Conclusion :  Conclusion 未來展望:  未來展望 UB是一個很新的研究 未來可望從這方面找出cancer、HD等疾病的治療方法 在這堂課要你學會的是:  在這堂課要你學會的是 UB是什麼?? Protein的degradation UB影響的層面 THANKS!!:  THANKS!!

Related presentations


Other presentations created by Abhil

oyster culture
03. 01. 2008
0 views

oyster culture

laser
02. 05. 2008
0 views

laser

electricity project
10. 10. 2007
0 views

electricity project

CAPM Nt
28. 04. 2008
0 views

CAPM Nt

futures
16. 04. 2008
0 views

futures

601presentation
29. 09. 2007
0 views

601presentation

RJ Iris Equity Seminar
03. 10. 2007
0 views

RJ Iris Equity Seminar

bubbles
03. 10. 2007
0 views

bubbles

weather jeopardy spanish
07. 10. 2007
0 views

weather jeopardy spanish

pc03
09. 10. 2007
0 views

pc03

IVACS2006 handout
09. 10. 2007
0 views

IVACS2006 handout

06 collaborating to improve ell
10. 10. 2007
0 views

06 collaborating to improve ell

lj
13. 10. 2007
0 views

lj

Lecture 1 Darwin vs God
15. 10. 2007
0 views

Lecture 1 Darwin vs God

NCMA Presentation
22. 10. 2007
0 views

NCMA Presentation

endangeredspecies ppt
12. 10. 2007
0 views

endangeredspecies ppt

mtom
24. 10. 2007
0 views

mtom

scaling
19. 10. 2007
0 views

scaling

p10
23. 10. 2007
0 views

p10

2007 Applicant Demographics
30. 10. 2007
0 views

2007 Applicant Demographics

WNV
21. 10. 2007
0 views

WNV

cells
20. 11. 2007
0 views

cells

conclusiones V1 sep28 2007
25. 10. 2007
0 views

conclusiones V1 sep28 2007

ap Cold War 07
23. 12. 2007
0 views

ap Cold War 07

10 Review
29. 12. 2007
0 views

10 Review

Isle Royale Simulation
01. 01. 2008
0 views

Isle Royale Simulation

structengr
04. 01. 2008
0 views

structengr

2005 02 07 Could Al Qaeda Win
07. 01. 2008
0 views

2005 02 07 Could Al Qaeda Win

td06030
15. 10. 2007
0 views

td06030

I DESC Japan
09. 10. 2007
0 views

I DESC Japan

section5 lec2
13. 11. 2007
0 views

section5 lec2

205w
03. 01. 2008
0 views

205w

Ceiling Fan Sales Training
23. 10. 2007
0 views

Ceiling Fan Sales Training

v war stuntman
19. 02. 2008
0 views

v war stuntman

HIMARS ENGLISHLANGUAGE
04. 03. 2008
0 views

HIMARS ENGLISHLANGUAGE

ING NYC Marathon 2007
12. 03. 2008
0 views

ING NYC Marathon 2007

K ICMCI as an NGO
20. 03. 2008
0 views

K ICMCI as an NGO

CPB750 TXT
03. 04. 2008
0 views

CPB750 TXT

Unit 4 Japan s Geography 1
07. 04. 2008
0 views

Unit 4 Japan s Geography 1

neither shall the sword
27. 02. 2008
0 views

neither shall the sword

solka fml 4 15 06 dj final
15. 11. 2007
0 views

solka fml 4 15 06 dj final

coface07
13. 04. 2008
0 views

coface07

AMurcko
17. 04. 2008
0 views

AMurcko

FACS borenstein Dec03
22. 04. 2008
0 views

FACS borenstein Dec03

mhtb
07. 11. 2007
0 views

mhtb

ç
10. 10. 2007
0 views

ç

Retroviruses105
15. 10. 2007
0 views

Retroviruses105

Krajweski Chapter 15 16
07. 05. 2008
0 views

Krajweski Chapter 15 16

0916 Branch 0730
02. 10. 2007
0 views

0916 Branch 0730

Lec5 3rd
30. 04. 2008
0 views

Lec5 3rd

pp angel cristian
01. 10. 2007
0 views

pp angel cristian

Guy Wormser
23. 10. 2007
0 views

Guy Wormser

From the Inside Looking Out
02. 05. 2008
0 views

From the Inside Looking Out

26 ple edgecock
17. 10. 2007
0 views

26 ple edgecock

rcdt 061127 05
10. 10. 2007
0 views

rcdt 061127 05

CAISModelGreenSchool
07. 03. 2008
0 views

CAISModelGreenSchool

Ordinamento Germania
16. 11. 2007
0 views

Ordinamento Germania

20041005 Adam Posen
09. 10. 2007
0 views

20041005 Adam Posen

A71 Quezada
01. 11. 2007
0 views

A71 Quezada

CAMET Report
22. 10. 2007
0 views

CAMET Report

workbench
08. 10. 2007
0 views

workbench

melderichtlinien
05. 10. 2007
0 views

melderichtlinien

APAN E culturePresentation 1 21
30. 10. 2007
0 views

APAN E culturePresentation 1 21

ANGELImplementationa tLCCC
01. 10. 2007
0 views

ANGELImplementationa tLCCC

Options Questionnaire 12 11 02
29. 10. 2007
0 views

Options Questionnaire 12 11 02

cancer nutri
04. 10. 2007
0 views

cancer nutri

SYSTEM 3 presentation
27. 09. 2007
0 views

SYSTEM 3 presentation

Souza parallel 3 1
12. 10. 2007
0 views

Souza parallel 3 1

Memorial 2007
18. 10. 2007
0 views

Memorial 2007

SIEl 2006
24. 10. 2007
0 views

SIEl 2006