曲度編著:細胞死亡通道悖論-Cell death pathway paradox

2010年第二篇：

曲 度譯：選擇性自噬：泛素介導的認同及其超越

Kraft C, Peter M, Hofmann K：Selective autophagy: ubiquitin-mediated recognition and beyond，Nat Cell Biol. 2010 Sep;12(9):836-41.
文章標題：選擇性自噬：泛素介導的認同及其超越.

Claudine Kraft and Matthias Peter are in the Institute of Biochemistry, ETH Zürich, Schafmattstrasse 18, CH-8093 Zürich, Switzerland. matthias.peter@bc.biol.ethz.ch.

Abstract
Eukaryotic cells use autophagy and the ubiquitin-proteasome system as their major protein degradation pathways. Whereas the ubiquitin-proteasome system is involved in the rapid degradation of proteins, autophagy pathways can selectively remove protein aggregates and damaged or excess organelles. Proteasome-mediated degradation requires previous ubiquitylation of the cargo, which is then recognized by ubiquitin receptors directing it to 26S proteasomes. Although autophagy has long been viewed as a random cytoplasmic degradation system, the involvement of ubiquitin as a specificity factor for selective autophagy is rapidly emerging. Recent evidence also suggests active crosstalk between proteasome-mediated degradation and selective autophagy. Here, we discuss the molecular mechanisms that link autophagy and the proteasome system, as well as the emerging roles of ubiquitin and ubiquitin-binding proteins in selective autophagy. On the basis of the evolutionary history of autophagic ubiquitin receptors, we propose a common origin for metazoan ubiquitin-dependent autophagy and the cytoplasm-to-vacuole targeting pathway of yeast.

摘要：
真核細胞使用自噬和泛素蛋白酶體系統，作為它們主要的蛋白質降解通道。儘管在蛋白質快速降解過程中涉及泛素蛋白酶體系統，但是細胞自噬通道能選擇地消除惡化和損壞的蛋白質以及過剩的細胞器。蛋白酶體介導的降解作用需要這種物質的先前泛素化作用，然後才認可通過泛素受體引導它至26S蛋白酶體。

雖然，細胞自噬長期以來被視作為一種隨機的細胞質降解體系，但是泛素的參與作用作為一種選擇性細胞自噬的特異性因子的觀點，正在迅速崛起。最近的研究證據也表明：在蛋白酶體介導降解作用與選擇性細胞自噬之間，存在一種活躍的對話。

在本文中，我們討論了那些與細胞自噬以及蛋白酶體系統相關聯的分子機制，並討論了在選擇性自噬作用中，泛素與泛素結合蛋白的新興作用。在自噬泛素受體的進化歷史基礎上，我們提出了一個針對後生動物的泛素依賴細胞自噬之共同起源（學說），和酵母以細胞質-空泡為標靶通道之說。

PMID: 20811356 [PubMed - in process]

tangdl2000選文2010-09-04 12:04
HUABIN 翻譯初稿 （2010。9。4 22：30）

2010年第五篇：

曲 度譯：吃就不死：巨自噬之歷史

Yang Z, Klionsky DJ.：Eaten alive: a history of macroautophagy. Nat Cell Biol. 2010 Sep;12(9):814-22.

the Life Sciences Institute, University of Michigan, 210 Washtenaw Avenue, Ann Arbor, MI 48109-2216, USA, the Department of Molecular, Cellular and Developmental Biology, 830 North University Avenue, Natural Science Building (Kraus) Ann Arbor, MI 48109-1048, USA and the Department of Biological Chemistry 1150 West Medical Center Drive, Ann Arbor, MI 48109-5606, USA.

Abstract
Macroautophagy (hereafter autophagy), or 'self-eating', is a conserved cellular pathway that controls protein and organelle degradation, and has essential roles in survival, development and homeostasis. Autophagy is also integral to human health and is involved in physiology, development, lifespan and a wide range of diseases, including cancer, neurodegeneration and microbial infection. Although research on this topic began in the late 1950s, substantial progress in the molecular study of autophagy has taken place during only the past 15 years. This review traces the key findings that led to our current molecular understanding of this complex process.

摘要：

巨自嗜「Macroautophagy」（以下簡稱自噬），或「自食」，是一種保留的細胞通道，其控制蛋白質和細胞器的降解，並在（生物機體）的生存，發展和動態平衡中起著一種基本的作用。

自噬對人類健康也是不可缺的，其涉及生理學，發育，壽命和多種疾病，包括癌症，細胞神經退行性變和微生物感染等。雖然這一科題研究始於20世紀50年代後期，但在過去15年中，細胞自噬的分子學研究方面取得重大進展。

這篇文獻綜述追索了那些關鍵的發現，後者導致我們目前對這一複雜過程的分子（生物學）觀點。

PMID: 20811353 [PubMed - in process]

tangdl2000選文2010-09-04 12:04
HUABIN 翻譯初稿 （2010。9。4 22：30）

2010年第十篇：

曲 度譯：在哺乳動物中細胞自噬的一些研究方法

Mizushima N, Yoshimori T, Levine B.：Methods in mammalian autophagy research. Cell. 2010 Feb 5;140(3):313-26.

Department of Physiology and Cell Biology, Tokyo Medical and Dental University, Tokyo 113-8519, Japan. nmizu.phy2@***.ac.jp

Abstract
Autophagy has been implicated in many physiological and pathological processes. Accordingly, there is a growing scientific need to accurately identify, quantify, and manipulate the process of autophagy. However, as autophagy involves dynamic and complicated processes, it is often analyzed incorrectly. In this Primer, we discuss methods to monitor autophagy and to modulate autophagic activity, with a primary focus on mammalian macroautophagy.

摘要：

自噬業已牽連許多生理和病理過程。因此，人們越來越需要科學性地準確識別，量化和操控的自噬的過程。然而，由於自噬涉及動態的複雜的過程，因此它在分析中往往處於不正確的狀態之中。

在這種背景下，我們討論那些監測細胞自噬和調節自嗜活性的方法，重點針對對哺乳動物的巨自噬「macroautophagy」作用。

PMID: 20144757

tangdl2000選文2010-09-04 12:04
HUABIN 翻譯初稿 （2010。9。4 22：30）

2000年第1篇：

曲度譯：自噬作為一種細胞降解作用的調控途徑

Klionsky DJ, Emr SD.：Autophagy as a regulated pathway of cellular degradation.
，Science. 2000 Dec 1;290(5497):1717-21.

Department of Biology, University of Michigan, 830 North University, Ann Arbor, MI 48109-1048, USA. klionsky@umich.edu

Abstract
Macroautophagy is a dynamic process involving the rearrangement of subcellular membranes to sequester cytoplasm and organelles for delivery to the lysosome or vacuole where the sequestered cargo is degraded and recycled. This process takes place in all eukaryotic cells.
It is highly regulated through the action of various kinases, phosphatases, and guanosine triphosphatases (GTPases). The core protein machinery that is necessary to drive formation and consumption of intermediates in the macroautophagy pathway includes a ubiquitin-like protein conjugation system and a protein complex that directs membrane docking and fusion at the lysosome or vacuole. Macroautophagy plays an important role in developmental processes, human disease, and cellular response to nutrient deprivation.

摘要：

巨自嗜「Macroautophagy」是一個動態的過程，其涉及到細胞內的膜之重新排列，以便隔離細胞質和細胞器，並輸送到溶酶體或液泡中去；在那裡，那些被隔離的物質被降解和再生。在所有的真核細胞中會發生這一過程。

通過各種激酶，磷酸酶與鳥苷三磷酸酶「guanosi triphosphatases」（GTP酶）的作用，這一過程被高度調控。

在巨自嗜「macroautophagy」途徑中，需要核蛋白機械性地參與，以便驅動中介物的形成和消耗；其包括一種泛素樣蛋白共軛體系和一種蛋白複合物，後者指導在溶酶體或空泡中的膜對接和融合。 巨自噬「Macroautophagy」在發育過程，人類疾病以及細胞對養分剝奪反應中起著一種重要的作用。

PMID: 11099404 [PubMed - indexed for MEDLINE]

tangdl2000選文2010-09-04 12:04
HUABIN 翻譯初稿 （2010。9。4 22：30）

2010年第七篇：

曲 度譯：解開在炎症和免疫之中的細胞死亡信號之密碼

Zitvogel L, Kepp O, Kroemer G.：Decoding cell death signals in inflammation and immunity，Cell. 2010 Mar 19;140 :798-804.

INSERM, Villejuif, France. zitvogel@igr.fr

Abstract
Dying cells release and expose at their surface molecules that signal to the immune system. We speculate that combinations of these molecules determine the route by which dying cells are engulfed and the nature of the immune response that their death elicits.

摘要：
垂死的細胞釋放和暴露出它們的表面分子，後者給免疫系統發出信號。我們推測這些分子的組合作用，決定了垂死細胞被吞噬以及免疫反應性質的途徑，並引導它們走向死亡。

PMID: 20303871


tangdl2000選文2010-09-04 12:04
HUABIN 翻譯初稿 （2010。9。4 22：30）

2010年第七篇：

曲 度譯：解開在炎症和免疫之中的細胞死亡信號之密碼

Zitvogel L, Kepp O, Kroemer G.：Decoding cell death signals in inflammation and immunity，Cell. 2010 Mar 19;140 :798-804.

INSERM, Villejuif, France. zitvogel@igr.fr

Abstract
Dying cells release and expose at their surface molecules that signal to the immune system. We speculate that combinations of these molecules determine the route by which dying cells are engulfed and the nature of the immune response that their death elicits.

摘要：
垂死的細胞釋放和暴露出它們的表面分子，後者給免疫系統發出信號。我們推測這些分子的組合作用，決定了垂死細胞被吞噬以及免疫反應性質的途徑，並引導它們走向死亡。

PMID: 20303871


tangdl2000選文2010-09-04 12:04
HUABIN 翻譯初稿 （2010。9。4 22：30）

2010年第三篇：

曲 度譯：自噬體膜的起源

Tooze SA, Yoshimori ：The origin of the autophagosomal membrane. Nat Cell Biol. 2010 Sep;12(9):831-5.

Sharon A. Tooze is in the Secretory Pathways Laboratory, London Research Institute Cancer Research UK, 44 Lincoln's Inn Fields, London, WC2A 3PX, U.K. sharon.tooze@cancer.org.uk.

Abstract
Macroautophagy is initiated by the formation of the phagophore (also called the isolation membrane). This membrane can both selectively and non-selectively engulf cytosolic components, grow and close around the sequestered components and then deliver them to a degradative organelle, the lysosome. Where this membrane comes from and how it grows is not well understood. Since the discovery of autophagy in the 1950s the source of the membrane has been investigated, debated and re-investigated, with the consensus view oscillating between a de novo assembly mechanism or formation from the membranes of the endoplasmic reticulum (ER) or the Golgi. In recent months, new information has emerged that both the ER and mitochondria may provide a membrane source, enlightening some older findings and revealing how complex the initiation of autophagy may be in mammalian cells.

------------------------------------------

英譯中摘要:

通過phagophore形成方式，啟動巨自嗜「Macroautophagy」，也稱為膜隔離。這種膜可以選擇性地和非選擇性地吞噬細胞質組成部分，生長並緊密地圍繞隔離成分，然後輸送它們到一種降解細胞器中去，後者即為溶酶體。

這種膜來自何處，已及它如何生長仍沒有充分的了解。自從20世紀50年代發現自噬現象以來，對這種膜的來源進行了研究，辯論和重新探索，大家的共識為從新組裝機制或者源自內質網（ER）或高爾基體之膜形成作用。

近幾個月來，所出現了新的信息，即內質網（ER）和線粒體可能提供了膜的來源，它啟示了某些舊的發現，並揭示在哺乳動物細胞中可能存在異常複雜的細胞自噬之啟動活動。

註：phagophore一詞不知如何中譯，敬請指教！

PMID: 20811355 [PubMed - in process]

tangdl2000選文2010-09-04 12:04
HUABIN 翻譯初稿 （2010。9。5- 22：30）

2010年第四篇：

曲 度譯：哺乳動物發育和分化中的自嗜現象

Mizushima N, Levine B.:Autophagy in mammalian development and differentiation;Nat Cell Biol. 2010 Sep;12(9):823-30.

Noboru Mizushima is in the Department of Physiology and Cell Biology, Tokyo Medical and Dental University, Tokyo 113-8519, Japan.

Abstract
It has been known for many decades that autophagy, a conserved lysosomal degradation pathway, is highly active during differentiation and development. However, until the discovery of the autophagy-related (ATG) genes in the 1990s, the functional significance of this activity was unknown. Initially, genetic knockout studies of ATG genes in lower eukaryotes revealed an essential role for the autophagy pathway in differentiation and development. In recent years, the analyses of systemic and tissue-specific knockout models of ATG genes in mice has led to an explosion of knowledge about the functions of autophagy in mammalian development and differentiation. Here we review the main advances in our understanding of these functions.

-------------------------------------------

英譯中摘要:

人們對細胞自噬的認識已經有幾十年之久，它在分化和發育過程中是一種保留的溶酶體降解途徑並非常活躍。

然而，直到20世紀90年代發現自噬相關基因（ATG），這種活動的功能性意義尚不明確。

最初，在較低等的真核生物的ATG基因之基因剔除研究中，發現在分化和發育過程中的一種細胞自噬途徑。

近幾年來，某些系統性分析以及在小鼠ATG基因的組織特異性基因敲除模型，已經導致了一種在哺乳動物發育和分化中細胞自噬功能方面的知識爆炸。本文中，我們回顧了我們所了解的這些功能之主要進展。

PMID: 20811354 [PubMed - in process]


tangdl2000選文2010-09-04 12:04
HUABIN 翻譯初稿 （2010。9。5- 22：30）

2010年第六篇：

高等真核生物細胞中監測自噬試驗之解釋與使用指南

Klionsky DJ, Abeliovich H, Agostinis P,ET AL:Guidelines for the use and interpretation of assays for monitoring autophagy in higher eukaryotes.Autophagy. 2008 Feb 16;4(2):151-75. Epub 2007 Nov 21.

Life Sciences Institute, University of Michigan, Ann Arbor, Michigan 48109-2216, USA. klionsky@umich.edu

Comment in:

Autophagy. 2008 Feb 16;4(2):139-40.

Abstract
Research in autophagy continues to accelerate,(1) and as a result many new scientists are entering the field. Accordingly, it is important to establish a standard set of criteria for monitoring macroautophagy in different organisms. Recent reviews have described the range of assays that have been used for this purpose.(2,3) There are many useful and convenient methods that can be used to monitor macroautophagy in yeast, but relatively few in other model systems, and there is much confusion regarding acceptable methods to measure macroautophagy in higher eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers of autophagosomes versus those that measure flux through the autophagy pathway; thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from fully functional autophagy that includes delivery to, and degradation within, lysosomes (in most higher eukaryotes) or the vacuole (in plants and fungi). Here, we present a set of guidelines for the selection and interpretation of the methods that can be used by investigators who are attempting to examine macroautophagy and related processes, as well as by reviewers who need to provide realistic and reasonable critiques of papers that investigate these processes. This set of guidelines is not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to verify an autophagic response.

------------------------------------------

摘要：

摘要

有關細胞自噬之研究持續性地增加（1），其結果是許多新的科學家正在進入這一領域。因此，在不同的生物機體中建立一套標準的監測巨自噬「macroautophagy」的準則規定，就具有重要意義。

最近的很多文獻複習業已描述已被使用於這一目的之檢測範圍。（2,3）

有許多有用的和方便的方法可用於監測酵母巨自嗜「macroautophagy」，但在其他模型系統中相對較少；此外，用於測試高等真核生物的巨自嗜「macroautophagy」，存在很多混淆的但看似可接受的方法。

需要強調的一個關鍵問題在於：在測量監測的自噬體數目與測量那些流過自噬途徑的自噬體數目之間，存在一種差異；這樣一來，巨自噬「macroautophagy」堆積，將導致自噬體「autophagosome」的聚集作用，需要從完全功能性自嗜的分化作用，其涉及輸送和降解，以及溶酶體（在大多數高等真核生物中）或液泡（植物和真菌液泡）。

本文中，我們提出一套指南，用於對這些方法的選擇和解釋；那些試圖檢測巨自嗜「macroautophagy」及其相關進程的研究人員可以使用之，此外，那些需要對這些研究過程的文章提供實際與合理的批評意見的審稿者可以使用之。

本套指南並不意味著是一種公式化的規則，因為適當檢測部分地取決於那些所需求的問題和正在使用的系統。此外，我們強調，沒有任何的檢測能保證在各種情況下都是最恰當的，我們強烈推薦使用多種檢測來驗證一種自噬反應。

PMID: 18188003 [PubMed - indexed for MEDLINE]

HUABIN 初譯稿

tangdl2000選文2010-09-04 12:04
HUABIN 翻譯初稿 （2010。9。4 22：30）

2010年第八篇：

曲 度譯：對癌症而言的線粒體關卡.

Galluzzi L, Morselli E, Kepp O, ET AL:Mitochondrial gateways to cancer
,Mol Aspects Med. 2010 Feb;31(1):1-20. Epub 2009 Aug 19.

INSERM, U848, Institut Gustave Roussy, PR1, 39 Rue Camille Desmoulins, F-94805 Villejuif, France.

Abstract
Mitochondria are required for cellular survival, yet can also orchestrate cell death. The peculiar biochemical properties of these organelles, which are intimately linked to their compartmentalized ultrastructure, provide an optimal microenvironment for multiple biosynthetic and bioenergetic pathways. Most intracellular ATP is generated by mitochondrial respiration, which also represents the most relevant source of intracellular reactive oxygen species. Mitochondria participate in a plethora of anabolic pathways, including cholesterol, cardiolipin, heme and nucleotide biosynthesis. Moreover, mitochondria integrate numerous pro-survival and pro-death signals, thereby exerting a decisive control over several biochemical cascades leading to cell death, in particular the intrinsic pathway of apoptosis. Therefore, it is not surprising that cancer cells often manifest the deregulation of one or several mitochondrial functions. The six classical hallmarks of cancer (i.e., limitless replication, self-provision of proliferative stimuli, insensitivity to antiproliferative signals, disabled apoptosis, sustained angiogenesis, invasiveness/metastatic potential), as well as other common features of tumors (i.e., avoidance of the immune response, enhanced anabolic metabolism, disabled autophagy) may directly or indirectly implicate deregulated mitochondria. In this review, we discuss several mechanisms by which mitochondria can contribute to malignant transformation and tumor progression.

-----------------------------------------

摘要：

線粒體對於細胞生存來說是必需的，但其也可以編排細胞死亡。這些細胞器奇特的生物化學特性是，其與隔離的超微結構是密切相連的，從而為多種生物合成和生物能量的途徑提供了一個最佳的微環境。

通過線粒體呼吸方式產生大部分細胞內的ATP，其也是細胞內活性氧類之最主要來源。線粒體參與了眾多的合成代謝途徑，其中包括膽固醇，心磷脂，血紅素和核苷酸生化合成。

此外，線粒體整合了許多的前-生存信號「pro-survival signals」和前-死亡信號「pro-death signals」，從而對一些生化級聯發揮了一種決定性的控制作用，導致細胞死亡，特別是內在的細胞凋亡途徑。因此，這一點也不奇怪，癌細胞往往體現了一種或幾種線粒體功能的管制放鬆。

癌症的經典的六個特點（即無限複製，增生性刺激的自我提供，對抗增殖信號的失敏感，凋亡失功，持續性血管生成，侵襲/轉移潛能），以及其他常見的腫瘤特徵（即逃避免疫反應，蛋白質同化代謝增強，自噬失功），均可能會直接或間接地牽涉線粒體之開放。在這篇綜述中，我們討論了一些機制，通過這些機制線粒體有助於惡性轉化和腫瘤的發展。

PMID: 19698742

tangdl2000選文2010-09-04 12:04
HUABIN 翻譯初稿 （2010。9。4 22：30）

2010年第九篇：

曲度譯:p53對細胞自噬的調節作用

Maiuri MC, Galluzzi L, Morselli E,ET AL:Autophagy regulation by p53
,Curr Opin Cell Biol. 2010 Apr;22(2):181-5. Epub 2010 Jan 13.

INSERM, U848, F-94805 Villejuif, France.

Abstract
Autophagy is an evolutionarily conserved catabolic pathway that is involved in numerous physiological processes and in multiple pathological conditions including cancer. Autophagy is regulated by an intricate network of signaling cascades that have not yet been entirely disentangled. Accumulating evidence indicates that p53, the best-characterized human tumor suppressor protein, can modulate autophagy in a dual fashion, depending on its subcellular localization. On the one hand, p53 functions as a nuclear transcription factor and transactivates proapoptotic, cell cycle-arresting and proautophagic genes. On the other hand, cytoplasmic p53 can operate at mitochondria to promote cell death and can repress autophagy via poorly characterized mechanisms. This review focuses on the recently discovered function of p53 as a master regulator of autophagy.

-----------------------------------------

摘要：

細胞自噬是一種進化上保守的代謝途徑，其涉及許多的生理過程和包括癌症在內的多種病理狀態。

通過一種尚未完全了解的級聯信號的複雜網路，可以調節自噬。

越來越多的證據表明：最佳特性的人類腫瘤抑制蛋白「p53」，可以雙重方式調控細胞自噬，其取決於它在亞細胞之定位。

一方面，p53的功能作用，起著一種核轉錄因子和經活化促凋亡「transactivates proapoptotic」，遏制細胞周期和促凋亡proautophagic基因之作用。

另一方面，細胞質p53能在線粒體操控，以便促進細胞死亡，並能通過不好特點的機制抑制細胞自噬。

這篇綜述重點討論，p53作為一種自噬的主要調控子，在最近所發現的功能。

PMID: 20044243


tangdl2000選文2010-09-04 12:04
HUABIN 翻譯初稿 （2010。9。4 22：30） 曲度譯:p53對細胞自噬的調節作用

2010年第十一篇：

曲 度譯：Beclin 1相互作用群

He C, Levine B.:The Beclin 1 interactome.Curr Opin Cell Biol. 2010 Apr;22(2):140-9. Epub 2010 Jan 22.

Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, TX 75390, United States.

Abstract
The mammalian ortholog of yeast Atg6/Vps30, Beclin 1, is an essential autophagy protein that has been linked to diverse biological processes, including immunity, development, tumor suppression, lifespan extension, and protection against certain cardiac and neurodegenerative diseases. In recent years, major advances have been made in identifying components of functionally distinct Beclin 1/class III phosphatidylinositol 3-kinase complexes, in characterizing the molecular regulation of interactions between Beclin 1 and the autophagy inhibitors, Bcl-2/BcL-X(L), and in uncovering a role for viral antagonists of Beclin 1 in viral pathogenesis. The rapidly growing list of components of the 'Beclin 1 interactome' supports a model in which autophagy, and potentially other membrane trafficking functions of Beclin 1, are governed by differential interactions with different binding partners in different physiological or pathophysiological contexts.

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摘要
哺乳動物同源的酵母Atg6/Vps30（Beclin 1），是一個重要的自噬蛋白。其與不同的生物過程相關，例如：包括免疫，發育，腫瘤抑制，壽命延長，以及對某些心臟和神經退行性疾病的保護。

近年來，在鑒定功能獨特的Beclin 1/class 三磷酸肌醇3-激酶複合物之成份方面，在Beclin 1與自噬抑制子「Bcl-2/BcL-X(L)」相互作用之分子調節特徵方面，在揭示病毒發病機制中Beclin 1作為病毒拮抗劑之作用方面，均取得了重大進展。

Beclin 1相互作用群成份之迅速發展的名單支持下列一種作用模式：在該模式中，自噬與潛在的其他膜的輸送Beclin 1之功能，是在不同的生理或病理生理情況下，通過不同的結合夥伴方式下不同的相互作用來完成之。

PMID: 20097051

tangdl2000選文2010-09-04 12:04
HUABIN 翻譯初稿 （2010。9。4 22：30）

1997年第1篇：

曲 度譯：Apg1p：在釀酒酵母自噬過程中所需的一種新的蛋白激酶
Matsuura A, Tsukada M, Wada Y,ET AL:Apg1p, a novel protein kinase required for the autophagic process in Saccharomyces cerevisiae.Gene. 1997 Jun 19;192(2):245-50

Department of Biology, Graduate School of Arts and Sciences, University of Tokyo, Komaba, Meguro-ku, Japan.

Abstract

Autophagic protein degradation includes bulk protein turnover with dynamic membrane reorganization, in which formation of novel organelles autophagosomes play key roles.

We have shown that Saccharomyces cerevisiae performs the autophagy in the vacuole, a lytic compartment of yeast, in response to various kinds of nutrient starvation.

Here we show that the APG1 gene, involved in the autophagic process in yeast, encodes a novel type of Ser/Thr protein kinase.

Our results provide direct evidence for involvement of protein phosphorylation in regulation of the autophagic process.

We found overall homology of Apglp with C. elegans Unc-51 protein, suggesting that homologous molecular mechanisms, conserved from unicellular to multicellular organisms, are involved in dynamic membrane flow.

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摘要：

細胞自噬蛋白質的降解作用涉及散在的蛋白質轉變成動態膜的重組作用；

在該作用中，新型細胞器自噬體的形成起著一種關鍵作用。

我們已經顯示，釀酒酵母形成液泡中的自嗜現象，與一種酵母裂解成分對各種營養缺乏狀態之反應相關。

在本文中，我們顯示APG1基因，在酵母自噬過程中，參與了一種新的類型的絲氨酸/蘇氨酸蛋白激酶（Ser/Thr protein kinase）的編碼。

我們的結果提供了在調控自噬過程中蛋白質磷酸化參與的直接證據。

我們發現了帶有UNC - 51蛋白之線蟲的整體同源性的，這就表明在動態膜流動中同源分子機制（有從單細胞到多細胞生物機體）都被涉及其中。

PMID: 9224897


tangdl2000選文2010-09-04 12:04
HUABIN 翻譯初稿 （2010。9。4 22：30）

1998年第1篇：

曲 度譯：beclin，一種新的Bcl-2相互作用蛋白能拮抗性保護致命性的Sindbis病毒性腦炎

Liang XH, Kleeman LK, Jiang HH,ET ALrotection against fatal Sindbis virus encephalitis by beclin, a novel Bcl-2-interacting protein.J Virol. 1998 Nov;72(11):8586-96.

Departments of Medicine, Columbia University College of Physicians and Surgeons, New York, New York 10032, USA.

Abstract

bcl-2, the prototypic cellular antiapoptotic gene, decreases Sindbis virus replication and Sindbis virus-induced apoptosis in mouse brains, resulting in protection against lethal encephalitis.

To investigate potential mechanisms by which Bcl-2 protects against central nervous system Sindbis virus infection, we performed a yeast two-hybrid screen to identify Bcl-2-interacting gene products in an adult mouse brain library.

We identified a novel 60-kDa coiled-coil protein, Beclin, which we confirmed interacts with Bcl-2 in mammalian cells, using fluorescence resonance energy transfer microscopy.

To examine the role of Beclin in Sindbis virus pathogenesis, we constructed recombinant Sindbis virus chimeras that express full-length human Beclin (SIN/beclin), Beclin lacking the putative Bcl-2-binding domain (SIN/beclinDeltaBcl-2BD), or Beclin containing a premature stop codon near the 5' terminus (SIN/beclinstop).

The survival of mice infected with SIN/beclin was significantly higher (71%) than the survival of mice infected with SIN/beclinDeltaBcl-2BD (9%) or SIN/beclinstop (7%) (P < 0.001).

The brains of mice infected with SIN/beclin had fewer Sindbis virus RNA-positive cells, fewer apoptotic cells, and lower viral titers than the brains of mice infected with SIN/beclinDeltaBcl-2BD or SIN/beclinstop.

These findings demonstrate that Beclin is a novel Bcl-2-interacting cellular protein that may play a role in antiviral host defense.

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摘要：

bcl - 2基因，這種典型細胞抗凋亡基因能減少在小鼠大腦中Sindbis病毒的複製和Sindbis病毒誘導的細胞凋亡，從而能夠拮抗性地保護致命性的腦炎。

為了探討Bcl – 2拮抗性保護中樞神經系統Sindbis病毒感染的潛在機制，我們進行了一種酵母雙雜交屏幕，以便鑒定在成年小鼠大腦庫中的Bcl - 2的相互作用基因的產物。

我們鑒定了一種新的60 - kDa的螺旋線圈蛋白質「Beclin」，我們通過採用熒光共振能量轉移顯微技術，證實其與哺乳動物細胞的相互作用。

為了探討Beclin在Sindbis病毒發病機制中的Beclin作用，我們構建和重組了Sindbis病毒嵌合體；其表達為全長人類Beclin（SIN/ beclin），缺乏推測Bcl - 2的結合域（SIN/beclin Delta Bcl-2BD）之Beclin，或含有鄰近5'端（SIN/ beclinstop）提前終止密碼子之Beclin 。

感染SIN/ beclin小鼠的存活率（71％）顯著高於感染SIN/beclinDeltaBcl-2BD（9％）； 或感染SIN/ beclinstop（7％），P <0.001。

感染SIN/ beclin小鼠的大腦存在較少的Sindbis病毒RNA陽性細胞，較少的凋亡細胞，

與感染SIN/beclinDeltaBcl-2BD或者SIN/ beclinstop的小鼠相比較，其大腦中Sindbis病毒的滴度較低。

這些結果表明：Beclin是一種新型的Bcl - 2相互作用的細胞蛋白，其可能參與了一種宿主抗病毒宿主之作用。

PMID: 9765397

tangdl2000選文2010-09-04 12:04
HUABIN 翻譯初稿 （2010。9。4 22：30）

2005年第1篇:

Levine B, Yuan J.：Autophagy in cell death: an innocent convict? J Clin Invest. 2005 Oct;115(10):2679-88.

曲 度譯:細胞死亡中的自噬：一個無辜的犯人?

Division of Infectious Diseases, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas 75390-9113, USA. beth.levin@utsouthwestern.edu

Erratum in:

J Clin Invest. 2006 Dec;116(12):3293.

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Abstract

The visualization of autophagosomes in dying cells has led to the belief that autophagy is a nonapoptotic form of programmed cell death.

This concept has now been evaluated using cells and organisms deficient in autophagy genes.

Most evidence indicates that, at least in cells with intact apoptotic machinery, autophagy is primarily a pro-survival rather than a pro-death mechanism.

This review summarizes the evidence linking autophagy to cell survival and cell death, the complex interplay between autophagy and apoptosis pathways, and the role of autophagy-dependent survival and death pathways in clinical diseases.

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整理之後:

摘要

垂死細胞中的自噬體可視化作用導致了對細胞自噬如下一種信念:即它是一種程序性細胞死亡的非凋亡「nonapoptotic」形式。

現在這個觀念已被使用在細胞和生物機體的自噬基因缺陷之評估當中。

多數證據表明：至少在完整凋亡機制的細胞之中，自噬作用主要是一種促-生存，而不是一種促-死亡的機制。

本文總結了那些細胞自噬與細胞生存以及細胞死亡相關的證據，細胞自噬與細胞凋亡的途徑之間的複雜相互作用，以及在臨床疾病中自噬依賴性生存和自噬依賴性死亡通道之作用。

HUABIN 初譯稿

2005年第1篇:

Levine B, Yuan J.：Autophagy in cell death: an innocent convict? J Clin Invest. 2005 Oct;115(10):2679-88.

曲 度譯:細胞死亡中的自噬：一個無辜的犯人?

Division of Infectious Diseases, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas 75390-9113, USA. beth.levin@utsouthwestern.edu

Erratum in:

J Clin Invest. 2006 Dec;116(12):3293.

----------------------------------------------------------------------------

Abstract

The visualization of autophagosomes in dying cells has led to the belief that autophagy is a nonapoptotic form of programmed cell death.

This concept has now been evaluated using cells and organisms deficient in autophagy genes.

Most evidence indicates that, at least in cells with intact apoptotic machinery, autophagy is primarily a pro-survival rather than a pro-death mechanism.

This review summarizes the evidence linking autophagy to cell survival and cell death, the complex interplay between autophagy and apoptosis pathways, and the role of autophagy-dependent survival and death pathways in clinical diseases.

---------------------------------------------------

整理之後:

摘要

垂死細胞中的自噬體可視化作用導致了對細胞自噬如下一種信念:即它是一種程序性細胞死亡的非凋亡「nonapoptotic」形式。

現在這個觀念已被使用在細胞和生物機體的自噬基因缺陷之評估當中。

多數證據表明：至少在完整凋亡機制的細胞之中，自噬作用主要是一種促-生存，而不是一種促-死亡的機制。

本文總結了那些細胞自噬與細胞生存以及細胞死亡相關的證據，細胞自噬與細胞凋亡的途徑之間的複雜相互作用，以及在臨床疾病中自噬依賴性生存和自噬依賴性死亡通道之作用。

HUABIN 初譯稿

2007年第1篇:

Klionsky DJ.：Autophagy: from phenomenology to molecular understanding in less than a decade. Nat Rev Mol Cell Biol. 2007 Nov;8(11):931-7.

曲度譯:細胞自噬--從現象到分子學了解不到十年

Life Sciences Institute, University of Michigan, 210 Washtenaw Avenue, Ann Arbor, Michigan 48109-2216, USA. klionsky@umich.edu

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Abstract

In 2000, it was suggested to me that "Autophagy will be the wave of the future; it will become the new apoptosis."

Few people would have agreed at the time, but this statement turned out to be prophetic, and this process of 'self-eating' rapidly exploded as a research field, as scientists discovered connections to cancer, neurodegeneration and even lifespan extension.

Amazingly, the molecular breakthroughs in autophagy have taken place during only the past decade.

--------------------------------------------------

整理之後;

摘要

在2000年內，有人對我建議：「自噬將是未來的趨勢，它將會成為新的細胞凋亡。」

在當時，很少人會同意這一觀點，但是這個說法已被證明是一種先知先覺；因為，對這種「自吃」進程之研究，迅速擴長成為一個研究領域；同時科學家們發現它與癌症，神經退行性變，甚至壽命延長均相聯繫。

令人驚訝的是，過去10年中，在自噬研究領域中已經發生分子學研究之突破。

HUABIN 初譯稿

2008年第1篇:

Mizushima N, Levine B, Cuervo AM，ET AL：Autophagy fights disease through cellular self-digestion. Nature. 2008 Feb 28;451(7182):1069-75.

曲 度譯:自噬通過細胞自我消化作用抵抗疾病

Department of Physiology and Cell Biology, Tokyo Medical and Dental University, Tokyo 113-8519, Japan.

----------------------------------------------------------------------------

Abstract
Autophagy, or cellular self-digestion, is a cellular pathway involved in protein and organelle degradation, with an astonishing number of connections to human disease and physiology.

For example, autophagic dysfunction is associated with cancer, neurodegeneration, microbial infection and ageing.

Paradoxically, although autophagy is primarily a protective process for the cell, it can also play a role in cell death. Understanding autophagy may ultimately allow scientists and clinicians to harness this process for the purpose of improving human health.

----------------------------------------------------------------------

整理之後:

摘要

細胞自噬（或細胞自我消化），是一種細胞通道，其涉及蛋白質和細胞器降解作用；並參與了數量驚人的人類疾病和生理過程。

例如，自噬功能障礙與癌症，神經退行性病變，微生物感染和老化相關。

矛盾的是，儘管自噬主要對於細胞起一種保護過程中，它也在細胞死亡中起著一定的作用。

認識細胞自噬現象，最終可能容許科學家和臨床醫生，利用這種過程以便達到改善人類健康之目的。

HUABIN 初譯稿

2008年第1篇:

Mizushima N, Levine B, Cuervo AM，ET AL：Autophagy fights disease through cellular self-digestion. Nature. 2008 Feb 28;451(7182):1069-75.

曲 度譯:自噬通過細胞自我消化作用抵抗疾病

Department of Physiology and Cell Biology, Tokyo Medical and Dental University, Tokyo 113-8519, Japan.

----------------------------------------------------------------------------

Abstract
Autophagy, or cellular self-digestion, is a cellular pathway involved in protein and organelle degradation, with an astonishing number of connections to human disease and physiology.

For example, autophagic dysfunction is associated with cancer, neurodegeneration, microbial infection and ageing.

Paradoxically, although autophagy is primarily a protective process for the cell, it can also play a role in cell death. Understanding autophagy may ultimately allow scientists and clinicians to harness this process for the purpose of improving human health.

----------------------------------------------------------------------

整理之後:

摘要

細胞自噬（或細胞自我消化），是一種細胞通道，其涉及蛋白質和細胞器降解作用；並參與了數量驚人的人類疾病和生理過程。

例如，自噬功能障礙與癌症，神經退行性病變，微生物感染和老化相關。

矛盾的是，儘管自噬主要對於細胞起一種保護過程中，它也在細胞死亡中起著一定的作用。

認識細胞自噬現象，最終可能容許科學家和臨床醫生，利用這種過程以便達到改善人類健康之目的。

HUABIN 初譯稿

2009年第1篇:

Green DR, Kroemer G.：Cytoplasmic functions of the tumour suppressor p53，Nature. 2009 Apr 30;458(7242):1127-30.

曲 度譯:腫瘤抑制因子p53的一些胞漿功能.

Department of Immunology, St Jude Children's Research Hospital, Memphis, Tennessee 38105, USA. douglas.green@stjude.org

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Abstract

The principal tumour-suppressor protein, p53, accumulates in cells in response to DNA damage, oncogene activation and other stresses.

It acts as a nuclear transcription factor that transactivates genes involved in apoptosis, cell cycle regulation and numerous other processes.

An emerging area of research unravels additional activities of p53 in the cytoplasm, where it triggers apoptosis and inhibits autophagy.

These previously unknown functions contribute to the mission of p53 as a tumour suppressor.

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整理之後:

摘要

積聚在細胞內主要的腫瘤抑制蛋白「p53」，負責對DNA損傷，癌基因激活和其他應激活動做出反應。

它作為一個核轉錄因子，這種經活化的基因涉及細胞凋亡，細胞周期調控和許多其他進程的活動。

一個新興的研究領域揭開了在細胞質中p53其他額外的活動，它觸發細胞凋亡和抑制細胞自噬。

這些以前未知的功能有助於p53基因擔負起一種腫瘤抑制因子的使命。

HUABIN 初譯稿