病理生理学进展课件：On to the road to degradation atherosclerosis and the proteasome.pptVIP

下载本文档

0
0
约1.59万字
约 63页
2023-05-11 发布于安徽
举报
版权申诉

病理生理学进展课件：On to the road to degradation atherosclerosis and the proteasome.ppt

1、原创力文档（book118）网站文档一经付费（服务费），不意味着购买了该文档的版权，仅供个人/单位学习、研究之用，不得用于商业用途，未经授权，严禁复制、发行、汇编、翻译或者网络传播等，侵权必究。。
2、本站所有内容均由合作方或网友上传，本站不对文档的完整性、权威性及其观点立场正确性做任何保证或承诺！文档内容仅供研究参考，付费前请自行鉴别。如您付费，意味着您自己接受本站规则且自行承担风险，本站不退款、不进行额外附加服务；查看《如何避免下载的几个坑》。如果您已付费下载过本站文档，您可以点击这里二次下载。
3、如文档侵犯商业秘密、侵犯著作权、侵犯人身权等，请点击“版权申诉”（推荐），也可以打举报电话：400-050-0827(电话支持时间：9:00-18:30)。
4、该文档为VIP文档，如果想要下载，成为VIP会员后，下载免费。
5、成为VIP后，下载本文档将扣除1次下载权益。下载后，不支持退款、换文档。如有疑问请联系我们。
6、成为VIP后，您将拥有八大权益，权益包括：VIP文档下载权益、阅读免打扰、文档格式转换、高级专利检索、专属身份标志、高级客服、多端互通、版权登记。
7、VIP文档为合作方或网友上传，每下载1次，网站将根据用户上传文档的质量评分、类型等，对文档贡献者给予高额补贴、流量扶持。如果你也想贡献VIP文档。上传文档

On to the road to degradation: atherosclerosis and the proteasome Background of ubiquitin-proteasome system (UPS).Structure, function, and regulation of UPS.Potential roles of UPS in atherosclerosis:The UPS in the initial stage of atherosclerosis.The UPS in the progression stage of atherosclerosis.The UPS in the complication stage of atherosclerosis.Proteasome inhibition-for better or worse in atherosclerosis?Introduction2 Legacy of UPS:1970s: 8.5KDa polypeptide; “ubiquitous immunopoietic polypeptide, (UBIP)” .Background3 BackgroundAvram Hershko Aaron Ciechanover Irwin Rose The 2004 Nobel Prize in Chemistry “for the discovery of ubiquitin-mediated protein degradation.”4 Legacy of UPS:1971-80: Avron Hershko, Aaran Ciechanover, Irwin Rose.Heat-stable polypeptide of ATP-dependent proteolytic system from reticulocytes. Reticulocyte crude extracts: fraction I :APF-1:ATP-dependent proteolysis factor 1→“ubiquitin”. (1979,1980,Hershko A and Ciechanover A.)Fraction II: (1) 450kDa: 26S proteasome; (2)E1-E3 conjugating enzymes. (1979,discovered by 3 scientists)Background5 Legacy of UPS:1971-80: Avron Hershko, Aaran Ciechanover, Irwin Rose.1981-83: multistep ubiquitin-tagging hypothesis.BackgroundProposed sequence of events in the ubiquitin-protein ligase system.6 Structure of UPS7 Regulation of UPSOn the level of E3 enzymes .Recognition patterns:N-end rule: “Destabilizing” N-terminal amino (Free basic, bulky hydrophic, or uncharged, e.g. arginine and lysine).Protein phosphorylation and hydroxylation. e.g. IκB and HIF-1α.Position of ubiquitin lysine residue. K48 for protein degradation and K63 for protein modulation.Ubiquitin activity regulation:Glucocorticoids, thyroid hormones, cytokines8 Function of UPSKiss of deathWaster disposer9 Function of UPSFunctional classProtein substratesPositive cell cycle regulatorsCyclin A,B,D,ENegative cell cycle regulatorsCDK inhibitors: p19INK4d , P21WAF1/Cip1K4dPro-apoptotic moleculesp53, Bax, Bid, Caspase 3, caspase 7Anti-apoptotic mole