{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,25]],"date-time":"2026-02-25T20:15:11Z","timestamp":1772050511343,"version":"3.50.1"},"reference-count":73,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2024,4,25]],"date-time":"2024-04-25T00:00:00Z","timestamp":1714003200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001736","name":"German-Israeli Foundation for Scientific Research and Development","doi-asserted-by":"publisher","award":["I-1471-414.13\/2018"],"award-info":[{"award-number":["I-1471-414.13\/2018"]}],"id":[{"id":"10.13039\/501100001736","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001736","name":"German-Israeli Foundation for Scientific Research and Development","doi-asserted-by":"publisher","award":["691517"],"award-info":[{"award-number":["691517"]}],"id":[{"id":"10.13039\/501100001736","id-type":"DOI","asserted-by":"publisher"}]},{"name":"START Program of the Medical Faculty of the RWTH Aachen University","award":["I-1471-414.13\/2018"],"award-info":[{"award-number":["I-1471-414.13\/2018"]}]},{"name":"START Program of the Medical Faculty of the RWTH Aachen University","award":["691517"],"award-info":[{"award-number":["691517"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>The unfolded protein response is an intricate system of sensor proteins in the endoplasmic reticulum (ER) that recognizes misfolded proteins and transmits information via transcription factors to either regain proteostasis or, depending on the severity, to induce apoptosis. The main transmembrane sensor is IRE1\u03b1, which contains cytoplasmic kinase and RNase domains relevant for its activation and the mRNA splicing of the transcription factor XBP1. Mast cell leukemia (MCL) is a severe form of systemic mastocytosis. The inhibition of IRE1\u03b1 in the MCL cell line HMC-1.2 has anti-proliferative and pro-apoptotic effects, motivating us to elucidate the IRE1\u03b1 interactors\/regulators in HMC-1.2 cells. Therefore, the TurboID proximity labeling technique combined with MS analysis was applied. Gene Ontology and pathway enrichment analyses revealed that the majority of the enriched proteins are involved in vesicle-mediated transport, protein stabilization, and ubiquitin-dependent ER-associated protein degradation pathways. In particular, the AAA ATPase VCP and the oncoprotein MTDH as IRE1\u03b1-interacting proteins caught our interest for further analyses. The pharmacological inhibition of VCP activity resulted in the increased stability of IRE1\u03b1 and MTDH as well as the activation of IRE1\u03b1. The interaction of VCP with both IRE1\u03b1 and MTDH was dependent on ubiquitination. Moreover, MTDH stability was reduced in IRE1\u03b1-knockout cells. Hence, pharmacological manipulation of IRE1\u03b1\u2013MTDH\u2013VCP complex(es) might enable the treatment of MCL.<\/jats:p>","DOI":"10.3390\/cells13090747","type":"journal-article","created":{"date-parts":[[2024,4,26]],"date-time":"2024-04-26T09:26:02Z","timestamp":1714123562000},"page":"747","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["TurboID-Based IRE1 Interactome Reveals Participants of the Endoplasmic Reticulum-Associated Protein Degradation Machinery in the Human Mast Cell Leukemia Cell Line HMC-1.2"],"prefix":"10.3390","volume":"13","author":[{"given":"Nabil","family":"Ahmed","sequence":"first","affiliation":[{"name":"Institute of Biochemistry and Molecular Immunology, Medical Faculty, RWTH Aachen University, 52074 Aachen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christian","family":"Preisinger","sequence":"additional","affiliation":[{"name":"Proteomics Facility, Interdisciplinary Centre for Clinical Research (IZKF), RWTH Aachen University, 52074 Aachen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas","family":"Wilhelm","sequence":"additional","affiliation":[{"name":"Institute of Biochemistry and Molecular Immunology, Medical Faculty, RWTH Aachen University, 52074 Aachen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7222-8686","authenticated-orcid":false,"given":"Michael","family":"Huber","sequence":"additional","affiliation":[{"name":"Institute of Biochemistry and Molecular Immunology, Medical Faculty, RWTH Aachen University, 52074 Aachen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,4,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"S31","DOI":"10.1016\/j.jaci.2019.02.004","article-title":"Regulation of the pleiotropic effects of tissue-resident mast cells","volume":"144","author":"Huber","year":"2019","journal-title":"J. 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