https://m2.mtmt.hu/ hun 2026-05-25 04:18 JournalArticle 33233590 VALIDATED true Funding Agency and Grant Number: New National Excellence Program of the Ministry for Culture and Innovation from the National Research, Development And Innovation Fund [UNKP-20-4-I-SE-32, UNKP-22-4-II-SE-21]; Semmelweis University [STIA-20-KF]; NKFIH [FK-134267]; Richter Gedeon Talentum foundation Funding text: This work was supported by UNKP-20-4-I-SE-32 and UNKP-22-4-II-SE-21 New National Excellence Program of the Ministry for Culture and Innovation from the source of the National Research, Development And Innovation Fund, by a STIA-20-KF of Semmelweis University. O.K., M.H. and B.H. were supported by NKFIH FK-134267 (National Research, Development and Innovation Office, Hungary). B.H. is supported by the Richter Gedeon Talentum foundation. 0 false 2026-05-22T07:29:58.597+0000 2023-03-07T12:42:14.880+0000 2022-11-14T15:40:32.813+0000 true 10019982 Sonnevend Kinga /api/admin/10019982 Admin true 10019982 2025-03-21T14:20:47.261+0000 2022-11-29T07:27:10.539+0000 true 10080205 Szalóky-Siki Ágnes /api/admin/10080205 Admin true true false true 24 24 /api/publicationtype/24 PublicationType 1 true 24 JournalArticle true 10000059 Article true 24 24 /api/publicationtype/24 PublicationType 1 true 24 JournalArticle /api/subtype/10000059 Szakcikk SubType 101 true 10000059 true 1 /api/category/1 Category true 1 Hajdú, Bence Fine-Tuning of mTORC1-ULK1-PP2A Regulatory Triangle Is Crucial for Robust Autophagic Response upon Cellular Stress true true /api/journal/10018879 REVIEWED true false 10018879 false 10018879 true 2218-273X 2218-273X Journal FOREIGN 12 11 1587 1587 15 2022 Autophagy-dependent cellular survival is tightly regulated by both kinases and phosphatases. While mTORC1 inhibits autophagy by phosphorylating ULK1, PP2A is able to remove this phosphate group from ULK1 and promotes the key inducer of autophagosome formation. However, ULK1 inhibits mTORC1, mTORC1 is able to down-regulate PP2A. In addition, the active ULK1 promotes PP2A via phosphorylation. We claim that these double-negative (mTORC1 –| PP2A –| mTORC1, mTORC1 –| ULK1 –| mTORC1) and positive (ULK1 -> PP2A -> ULK1) feedback loops are all necessary for the robust, irreversible decision making process between the autophagy and non-autophagy states. We approach our scientific analysis from a systems biological perspective by applying both theoretical and molecular biological techniques. For molecular biological experiments, HEK293T cell line is used, meanwhile the dynamical features of the regulatory network are described by mathematical modelling. In our study, we explore the dynamical characteristic of mTORC1-ULK1-PP2A regulatory triangle in detail supposing that the positive feedback loops are essential to manage a robust cellular answer upon various cellular stress events (such as mTORC1 inhibition, starvation, PP2A inhibition or ULK1 silencing). We confirm that active ULK1 can up-regulate PP2A when mTORC1 is inactivated. By using theoretical analysis, we explain the importance of cellular PP2A level in stress response mechanism. We proved both experimentally and theoretically that PP2A down-regulation (via addition of okadaic acid) might generate a periodic repeat of autophagy induction. Understanding how the regulation of the cell survival occurs with the precise molecular balance of ULK1-mTORC1-PP2A in autophagy, is highly relevant in several cellular stress-related diseases (such as neurodegenerative diseases or diabetes) and might help to promote advanced therapies in the near future, too. 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(PPKE / ITK) 5 16 3 5 0 true Language 10002 /api/language/10002 Angol English true 2 true PersonAuthorship 104249356 /api/authorship/104249356 1 0.2 true false false Author 10079242 /api/author/10079242 Hajdú Bence true true Hajdú Bence true false false AuthorshipType 1 /api/authorshiptype/1 0 true 0 true false true PersonAuthorship 104249357 /api/authorship/104249357 2 0.2 false false false Author 10057448 /api/author/10057448 Holczer Marianna true 10057448 true Holczer Marianna true false false AuthorshipType 1 /api/authorshiptype/1 0 true 0 true false true PersonAuthorship 104249358 /api/authorship/104249358 3 0.2 false false false Author 10080218 /api/author/10080218 Horváth Gergely true true Horváth Gergely true false false AuthorshipType 1 /api/authorshiptype/1 0 true 0 true false true PersonAuthorship 104249359 /api/authorship/104249359 4 0.2 false false false Author 10000614 /api/author/10000614 Szederkényi Gábor true 10000614 true Szederkényi Gábor true false false 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src="/frontend/resources/grid/publication-citation-icon.png"> <div class="autype autype0"> <span class="author-name" mtid="10079242"><a href="/gui2/?type=authors&mode=browse&sel=10079242" target="_blank">Hajdú Bence (<span class="authorship-author-name">Hajdú Bence</span> <span class="authorAux-mtmt"> Biokémia</span>) </a> </span> <span class="author-affil"><span title="Semmelweis Egyetem">SE</span>/<span title="Általános Orvostudományi Kar">AOK</span>/<span title="Intézet">I</span>/<span title="Biokémiai és Molekuláris Biológiai Intézet">BMBI</span>/Molekuláris Biológiai Tanszék</span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" mtid="10057448"><a href="/gui2/?type=authors&mode=browse&sel=10057448" target="_blank">Holczer Marianna (<span class="authorship-author-name">Holczer Marianna</span> <span class="authorAux-mtmt"> Biokémia</span>) </a> </span> <span class="author-affil"><span title="Semmelweis Egyetem">SE</span>/<span title="Általános Orvostudományi Kar">AOK</span>/<span title="Intézet">I</span>/<span title="Biokémiai és Molekuláris Biológiai Intézet">BMBI</span>/Molekuláris Biológiai Tanszék</span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" mtid="10080218"><a href="/gui2/?type=authors&mode=browse&sel=10080218" target="_blank">Horváth Gergely (<span class="authorship-author-name">Horváth Gergely</span> <span class="authorAux-mtmt"> informatikai tudományok</span>) </a> </span> <span class="author-affil"><span title="Pázmány Péter Katolikus Egyetem">PPKE</span>/<span title="Információs Technológiai és Bionikai Kar">ITK</span>/Roska Tamás Műszaki és Természettudományi Doktori Iskola</span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" mtid="10000614"><a href="/gui2/?type=authors&mode=browse&sel=10000614" target="_blank">Szederkényi Gábor (<span class="authorship-author-name">Szederkényi Gábor</span> <span class="authorAux-mtmt"> Nemlineáris dinamikus rendszerek</span>) </a> </span> <span class="author-affil"><span title="Pázmány Péter Katolikus Egyetem">PPKE</span>/Információs Technológiai és Bionikai Kar</span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" mtid="10026330"><a href="/gui2/?type=authors&mode=browse&sel=10026330" target="_blank">Kapuy Orsolya ✉ (<span class="authorship-author-name">Kapuy Orsolya</span> <span class="authorAux-mtmt"> Biokémia</span>) </a> </span> <span class="author-affil"><span title="Semmelweis Egyetem">SE</span>/<span title="Általános Orvostudományi Kar">AOK</span>/<span title="Intézet">I</span>/<span title="Biokémiai és Molekuláris Biológiai Intézet">BMBI</span>/Molekuláris Biológiai Tanszék</span> </div> </div> <div class="title"><a href="/gui2/?mode=browse&params=publication;33233590" target="_blank">Fine-Tuning of mTORC1-ULK1-PP2A Regulatory Triangle Is Crucial for Robust Autophagic Response upon Cellular Stress</a></div> <div> <span class="journal-title">BIOMOLECULES</span> <span class="journal-issn">(<a target="_blank" href="https://portal.issn.org/resource/ISSN/2218-273X">2218-273X</a> <a target="_blank" href="https://portal.issn.org/resource/ISSN/2218-273X">2218-273X</a>)</span>: <span class="journal-volume">12</span> <span class="journal-issue">11</span> <span class="page"> Paper 1587. 15 p. </span> <span class="year">(2022)</span> </div> <div class="pub-footer"> <span class="language" xmlns="http://www.w3.org/1999/html">Nyelv: Angol | </span> <span class="identifiers"> <span class="id identifier oa_GOLD" title=" Gold "> <a style="color:blue" title="10.3390/biom12111587" target="_blank" href="https://doi.org/10.3390/biom12111587"> DOI </a> </span> <span class="id identifier oa_none" title="none"> <a style="color:blue" title="000882701700001" target="_blank" href="https://www.webofscience.com/wos/woscc/full-record/000882701700001"> WoS </a> </span> <span class="id identifier oa_none" title="none"> <a style="color:blue" title="85141773803" target="_blank" href="http://www.scopus.com/record/display.url?origin=inward&eid=2-s2.0-85141773803"> Scopus </a> </span> <span class="id identifier oa_none" title="none"> <a style="color:blue" title="36358936" target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=36358936&dopt=Abstract"> PubMed </a> </span> </span> <OnlyViewableByAuthor><div class="ratings"> <div class="journal-subject">Folyóirat szakterülete: Scopus - Biochemistry&nbsp;&nbsp;&nbsp;SJR indikátor:&nbsp;Q1</div> <div class="journal-subject">Folyóirat szakterülete: Scopus - Molecular Biology&nbsp;&nbsp;&nbsp;SJR indikátor:&nbsp;Q2</div> </div></OnlyViewableByAuthor> <div class="publication-citation" style="margin-left: 0.5cm;"> <span title="Nyilvános idézőközlemények összesen, említések nélkül" class="citingPub-count">Nyilvános idéző összesen: 12</span> | Független: 10 | Függő: 2 | Nem jelölt: 0 | WoS jelölt: 12 | Scopus jelölt:&nbsp;10 | WoS/Scopus jelölt:&nbsp;12 | DOI jelölt:&nbsp;12 </div> <div class="publication-citation"> <a target="_blank" href="/api/publication?cond=citations.related;eq;33233590&sort=publishedYear,desc&sort=title"> Idézett közlemények száma: 5 </a> </div> <div class="mtid"><span class="long-pub-mtid">Közlemény: 33233590</span> | <span class="status-data status-VALIDATED"> Egyeztetett </span> Forrás Idéző | <span class="type-subtype">Folyóiratcikk ( Szakcikk ) </span> | <span class="pub-category">Tudományos</span> | <span class="publication-sourceOfData">kézi felvitel</span> </div> <div class="funder"> (ÚNKP-20-4-I-SE-32), (ÚNKP-22-4-II-SE-21), (STIA-20-KF), (FK-134267), Richter Gedeon Talentum Foundation </div> <div class="lastModified">Utolsó módosítás: 2023.03.07. 13:42 Sifter Viktória (PPKE ITK admin 5) </div> <pre class="comment" style="margin-top: 0; margin-bottom: 0;"><u>Megjegyzés</u>: Funding Agency and Grant Number: New National Excellence Program of the Ministry for Culture and Innovation from the National Research, Development And Innovation Fund [UNKP-20-4-I-SE-32, UNKP-22-4-II-SE-21]; Semmelweis University [STIA-20-KF]; NKFIH [FK-134267]; Richter Gedeon Talentum foundation Funding text: This work was supported by UNKP-20-4-I-SE-32 and UNKP-22-4-II-SE-21 New ...</pre> </div></div>