{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T20:40:53Z","timestamp":1788813653116,"version":"build-2803163510"},"reference-count":35,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2019,3,11]],"date-time":"2019-03-11T00:00:00Z","timestamp":1552262400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001700","name":"Ministry of Education, Culture, Sports, Science and Technology","doi-asserted-by":"publisher","award":["Scientific Research on Priority Areas"],"award-info":[{"award-number":["Scientific Research on Priority Areas"]}],"id":[{"id":"10.13039\/501100001700","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007449","name":"Takeda Science Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007449","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molecular Carcinogenesis"],"published-print":{"date-parts":[[2019,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>KIF1B\u03b2, a member of the kinesin superfamily of motor proteins, is a haploinsufficient tumor suppressor mapped to chromosome 1p36.2, which is frequently deleted in neural crest\u2013derived tumors, including neuroblastoma and pheochromocytoma. While KIF1B\u03b2 acts downstream of the nerve growth factor (NGF) pathway to induce apoptosis, further molecular functions of this gene product have largely been unexplored. In this study, we report that KIF1B\u03b2 destabilizes the morphological structure of mitochondria, which is critical for cell survival and apoptosis. We identified YME1L1, a mitochondrial metalloprotease responsible for the cleavage of the mitochondrial GTPase OPA1, as a physical interacting partner of KIF1B\u03b2. KIF1B\u03b2 interacted with YME1L1 through its death\u2010inducing region, as initiated the protease activity of YME1L1 to cleave the long forms of OPA1, resulting in mitochondrial fragmentation. Overexpression of YME1L1 promoted apoptosis, while knockdown of YME1L1 promoted cell growth. High <jats:italic>YME1L1<\/jats:italic> expression was significantly associated with a better prognosis in neuroblastoma. Furthermore, in NGF\u2010deprived PC12 cells, KIF1B\u03b2 and YME1L1 were upregulated, accompanied by mitochondrial fragmentation and apoptotic cell death. Small interfering RNA\u2013mediated knockdown of either protein alone, however, remarkably inhibited the NGF depletion\u2013induced apoptosis. Our findings indicate that tumor suppressor KIF1B\u03b2 plays an important role in intrinsic mitochondria\u2013mediated apoptosis through the regulation of structural and functional dynamics of mitochondria in collaboration with YME1L1. Dysfunction of the KIF1B\u03b2\/YME1L1\/OPA1 mechanism may be involved in malignant biological features of neural crest\u2013derived tumors as well as the initiation and progression of neurodegenerative diseases.<\/jats:p>","DOI":"10.1002\/mc.22997","type":"journal-article","created":{"date-parts":[[2019,3,12]],"date-time":"2019-03-12T04:17:23Z","timestamp":1552364243000},"page":"1134-1144","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["Tumor suppressor KIF1B\u03b2 regulates mitochondrial apoptosis in collaboration with YME1L1"],"prefix":"10.1002","volume":"58","author":[{"given":"Koji","family":"Ando","sequence":"first","affiliation":[{"name":"Division of Biochemistry and Innovative Cancer Therapeutics Chiba Cancer Center Research Institute Chiba Japan"},{"name":"Department of Surgery and Science Graduate School of Medical Sciences, Kyushu University Fukuoka 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