{"created":"2023-06-20T13:21:15.270252+00:00","id":1372,"links":{},"metadata":{"_buckets":{"deposit":"859f7d49-cee3-44af-98a8-28837eb44f50"},"_deposit":{"created_by":1,"id":"1372","owners":[1],"pid":{"revision_id":0,"type":"depid","value":"1372"},"status":"published"},"_oai":{"id":"oai:ir.soken.ac.jp:00001372","sets":["2:430:27"]},"author_link":["9720","9721","9722"],"item_1_creator_2":{"attribute_name":"著者名","attribute_type":"creator","attribute_value_mlt":[{"creatorNames":[{"creatorName":"久万, 亜紀子"}],"nameIdentifiers":[{}]}]},"item_1_creator_3":{"attribute_name":"フリガナ","attribute_type":"creator","attribute_value_mlt":[{"creatorNames":[{"creatorName":"クマ, アキコ"}],"nameIdentifiers":[{}]}]},"item_1_date_granted_11":{"attribute_name":"学位授与年月日","attribute_value_mlt":[{"subitem_dategranted":"2003-03-24"}]},"item_1_degree_grantor_5":{"attribute_name":"学位授与機関","attribute_value_mlt":[{"subitem_degreegrantor":[{"subitem_degreegrantor_name":"総合研究大学院大学"}]}]},"item_1_degree_name_6":{"attribute_name":"学位名","attribute_value_mlt":[{"subitem_degreename":"博士（理学）"}]},"item_1_description_12":{"attribute_name":"要旨","attribute_value_mlt":[{"subitem_description":"In eukaryotic cells, the majority of intracellular bulk degradation occurs in the vacuole/lysosome, an acidic compartment that contains various hydrolytic enzymes.  Autophagy is the main pathway to deliver cytoplasmic components to the vacuole in yeast, or to the lysosome in mammalian cells, for degradation.  In this process, portion of cytoplasm are sequestered within the double-membrane structure termed autophagosome, which subsequently fuses with the vacuole/lysosome.  The sequestered components are, then, degraded by the vacuolar or lysosomal hydrolases for reuse.  The best-known role of autophagy is a cellular survival response to starvation, but it also plays important roles in developmental process and cell differentiation.  Taking advantage of yeast genetics, autophagy defective mutants (apg) were isolated and so far 15 APG genes have been cloned.  All of them seem to be involved in the step of autophagosome formation.  During the characterization of Apg proteins, a ubiquitin-like conjugation system, the Apgl2 system, was found to be essential for autophagy.  In this system, Apg12 is covalently bound to Apg5, which is catalyzed by Apg7 and Apgl0.  Mammalian homologues of Apgl2 and Apg5 have been identified and undergo a similar covalent linkage, indicating that this conjugation system is conserved in mammalian cells.  Studies using mammalian cells further revealed that the Apg12-Apg5 conjugate localized to pre-autopagosomal membrane and is required for elongation of the membrane to form a complete spherical autophagosome.  But the exact molecular role of the Apg12-Apg5 conjugate is still unknown.  Recently, Apgl6 was found to interact with the Apg12-Apg5 conjugate in yeast.  Apg16 is a 150-amino acid protein that contains a carboxyl-terminal coiled-coil motif.  Since Apg16 is the only molecule identified to interact with the Apg12-Apg5 conjugate and required for function of the conjugate, further characterization of Apg16 would provide valuable insights into the molecular role of the Apg12-Apg5 conjugate.  In this study, she found that Apg12-Apg5 conjugate formed a ～350-kDa complex with Apg16 in the cytosol of yeast cells, irrespective of autophagy induction.  As Apg16 formed homo-oligomer through the coiled-coil region and cross-linked Apg12-Apg5, she generated an in vivo system that allows us to control the oligomerization state of Apg16.  With this system, she demonstrated concretely that formation of the ～350-kDa complex depends on oligomerization of Apg16 and formation of this complex is required for autophagy in yeast.<br />  Although the Apg12-Apg5 conjugation system is highly conserved among eukaryotes, there is no significant homologue of Apg16.  In mammalian cells, the Apg12-Apg5 conjugate forms a ～800-kDa complex, much larger than the yeast Apg12-Apg5･Apg16 complex.  Purification of this ～800-kDa complex identified a novel Apg5-interacting protein containing seven WD repeats.  She demonstrated that this newly WD repeat protein, named Apg16L, is a functional counterpart of yeast Apg16.  Mouse Apg16L interacts with Apg5 at its amino-terminal region and forms a homo-oligomer through its coiled-coil region to form the ～800-kDa complex as yeast Apg16.  Apg16L associates with pre-autophagosomal membrane with the Apg12-Apg5 conjugate, suggesting that the ～80O-kDa complex functions in autophagosome formations in mammalian cells.<br />  Since multiple homologues of Apg16L exist in higher eukaryotes, the autophagic machinery is well conserved through evolution.  On the other hand, WD domain, which is thought to be a platform for protein-protein interaction, is not found in yeast Apg16.  As the WD domain of Apg16L is not required for interaction with Apg5 and homo-oligomerization, the ～800-kDa complex is expected to interact with other proteins.  Identification of such proteins would be helpful to understand the molecular mechanism of the Apg12-Apg5 conjugate in autophagosome formation.","subitem_description_type":"Other"}]},"item_1_description_18":{"attribute_name":"フォーマット","attribute_value_mlt":[{"subitem_description":"application/pdf","subitem_description_type":"Other"}]},"item_1_description_7":{"attribute_name":"学位記番号","attribute_value_mlt":[{"subitem_description":"総研大甲第690号","subitem_description_type":"Other"}]},"item_1_select_14":{"attribute_name":"所蔵","attribute_value_mlt":[{"subitem_select_item":"有"}]},"item_1_select_8":{"attribute_name":"研究科","attribute_value_mlt":[{"subitem_select_item":"生命科学研究科"}]},"item_1_select_9":{"attribute_name":"専攻","attribute_value_mlt":[{"subitem_select_item":"X2 分子生物機構論専攻"}]},"item_1_text_10":{"attribute_name":"学位授与年度","attribute_value_mlt":[{"subitem_text_value":"2002"}]},"item_creator":{"attribute_name":"著者","attribute_type":"creator","attribute_value_mlt":[{"creatorNames":[{"creatorName":"KUMA, Akiko","creatorNameLang":"en"}],"nameIdentifiers":[{}]}]},"item_files":{"attribute_name":"ファイル情報","attribute_type":"file","attribute_value_mlt":[{"accessrole":"open_date","date":[{"dateType":"Available","dateValue":"2016-02-17"}],"displaytype":"simple","filename":"甲690_要旨.pdf","filesize":[{"value":"241.4 kB"}],"format":"application/pdf","licensetype":"license_11","mimetype":"application/pdf","url":{"label":"要旨・審査要旨 / Abstract, Screening Result","url":"https://ir.soken.ac.jp/record/1372/files/甲690_要旨.pdf"},"version_id":"59430b89-bb39-4af5-9010-f97aab837728"},{"accessrole":"open_date","date":[{"dateType":"Available","dateValue":"2016-02-17"}],"displaytype":"simple","filename":"甲690_本文.pdf","filesize":[{"value":"6.1 MB"}],"format":"application/pdf","licensetype":"license_11","mimetype":"application/pdf","url":{"label":"本文","url":"https://ir.soken.ac.jp/record/1372/files/甲690_本文.pdf"},"version_id":"8afb04e4-70d1-407d-8314-4ebb99b1a2c1"}]},"item_language":{"attribute_name":"言語","attribute_value_mlt":[{"subitem_language":"eng"}]},"item_resource_type":{"attribute_name":"資源タイプ","attribute_value_mlt":[{"resourcetype":"thesis","resourceuri":"http://purl.org/coar/resource_type/c_46ec"}]},"item_title":"Studies on the Apg12-Apg5・Apg16 complex essential for autophagy","item_titles":{"attribute_name":"タイトル","attribute_value_mlt":[{"subitem_title":"Studies on the Apg12-Apg5・Apg16 complex essential for autophagy"},{"subitem_title":"Studies on the Apg12-Apg5・Apg16 complex essential for autophagy","subitem_title_language":"en"}]},"item_type_id":"1","owner":"1","path":["27"],"pubdate":{"attribute_name":"公開日","attribute_value":"2010-02-22"},"publish_date":"2010-02-22","publish_status":"0","recid":"1372","relation_version_is_last":true,"title":["Studies on the Apg12-Apg5・Apg16 complex essential for autophagy"],"weko_creator_id":"1","weko_shared_id":1},"updated":"2023-06-20T14:44:36.566622+00:00"}