{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T08:01:13Z","timestamp":1790755273836,"version":"4.1.0"},"reference-count":47,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2015,12,14]],"date-time":"2015-12-14T00:00:00Z","timestamp":1450051200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Marine Drugs"],"abstract":"<jats:p>MytiLec; a novel lectin isolated from the Mediterranean mussel (Mytilus galloprovincialis); shows strong binding affinity to globotriose (Gb3: Gal\u03b11-4Gal\u03b21-4Glc). MytiLec revealed \u03b2-trefoil folding as also found in the ricin B-subunit type (R-type) lectin family, although the amino acid sequences were quite different. Classification of R-type lectin family members therefore needs to be based on conformation as well as on primary structure. MytiLec specifically killed Burkitt's lymphoma Ramos cells, which express Gb3. Fluorescein-labeling assay revealed that MytiLec was incorporated inside the cells. MytiLec treatment of Ramos cells resulted in activation of both classical MAPK\/ extracellular signal-regulated kinase and extracellular signal-regulated kinase (MEK-ERK) and stress-activated (p38 kinase and JNK) Mitogen-activated protein kinases (MAPK) pathways. In the cells, MytiLec treatment triggered expression of tumor necrosis factor (TNF)-\u03b1 (a ligand of death receptor-dependent apoptosis) and activation of mitochondria-controlling caspase-9 (initiator caspase) and caspase-3 (activator caspase). Experiments using the specific MEK inhibitor U0126 showed that MytiLec-induced phosphorylation of the MEK-ERK pathway up-regulated expression of the cyclin-dependent kinase inhibitor p21, leading to cell cycle arrest and TNF-\u03b1 production. Activation of caspase-3 by MytiLec appeared to be regulated by multiple different pathways. Our findings, taken together, indicate that the novel R-type lectin MytiLec initiates programmed cell death of Burkitt\u2019s lymphoma cells through multiple pathways (MAPK cascade, death receptor signaling; caspase activation) based on interaction of the lectin with Gb3-containing glycosphingolipid-enriched microdomains on the cell surface.<\/jats:p>","DOI":"10.3390\/md13127071","type":"journal-article","created":{"date-parts":[[2015,12,14]],"date-time":"2015-12-14T02:57:29Z","timestamp":1450061849000},"page":"7377-7389","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":55,"title":["MytiLec, a Mussel R-Type Lectin, Interacts with Surface Glycan Gb3 on Burkitt\u2019s Lymphoma Cells to Trigger Apoptosis through Multiple Pathways"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4715-9022","authenticated-orcid":false,"given":"Imtiaj","family":"Hasan","sequence":"first","affiliation":[{"name":"Department of Life and Environmental System Science, Graduate School of NanoBio Sciences, Yokohama City University, 22-2 Seto, Kanazawa-ku, Yokohama 236-0027, Japan"},{"name":"Department of Biochemistry and Molecular Biology, Faculty of Science, University of Rajshahi, Rajshahi-6205, Bangladesh"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shigeki","family":"Sugawara","sequence":"additional","affiliation":[{"name":"Division of Cell Recognition Study, Institute of Molecular Biomembrane and Glycobiology, Tohoku Pharmaceutical University, 4-4-1 Komatsushima, Aoba-ku, Sendai 981-8558, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuki","family":"Fujii","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Faculty of Pharmaceutical Science, Nagasaki International University, 2825-7 Huis Ten Bosch, Sasebo, Nagasaki 859-3298, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasuhiro","family":"Koide","sequence":"additional","affiliation":[{"name":"Department of Life and Environmental System Science, Graduate School of NanoBio Sciences, Yokohama City University, 22-2 Seto, Kanazawa-ku, Yokohama 236-0027, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daiki","family":"Terada","sequence":"additional","affiliation":[{"name":"Graduate School of Medical Life Science, Yokohama City University, 1-7-29 Suehiro-cho, Tsurumi-ku, Yokohama 230-0045, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naoya","family":"Iimura","sequence":"additional","affiliation":[{"name":"Department of Life and Environmental System Science, Graduate School of NanoBio Sciences, Yokohama City University, 22-2 Seto, Kanazawa-ku, Yokohama 236-0027, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshiyuki","family":"Fujiwara","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Faculty of Pharmaceutical Science, Nagasaki International University, 2825-7 Huis Ten Bosch, Sasebo, Nagasaki 859-3298, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keisuke","family":"Takahashi","sequence":"additional","affiliation":[{"name":"Graduate School of Agricultural Science, Tohoku University, 1-1 Amamiya-machi, Tsutsumidori, Aoba-ku, Sendai 230-0045, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nobuhiko","family":"Kojima","sequence":"additional","affiliation":[{"name":"Department of Life and Environmental System Science, Graduate School of NanoBio Sciences, Yokohama City University, 22-2 Seto, Kanazawa-ku, Yokohama 236-0027, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sultana","family":"Rajia","sequence":"additional","affiliation":[{"name":"Department of Life and Environmental System Science, Graduate School of NanoBio Sciences, Yokohama City University, 22-2 Seto, Kanazawa-ku, Yokohama 236-0027, Japan"},{"name":"Department of Natural Science, Varendra University, Rajshahi-6204, Bangladesh"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7964-9117","authenticated-orcid":false,"given":"Sarkar","family":"Kawsar","sequence":"additional","affiliation":[{"name":"Department of Life and Environmental System Science, Graduate School of NanoBio Sciences, Yokohama City University, 22-2 Seto, Kanazawa-ku, Yokohama 236-0027, Japan"},{"name":"Department of Chemistry, Faculty of Sciences, University of Chittagong, Chittagong-4331, Bangladesh"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Kanaly","sequence":"additional","affiliation":[{"name":"Department of Life and Environmental System Science, Graduate School of NanoBio Sciences, Yokohama City University, 22-2 Seto, Kanazawa-ku, Yokohama 236-0027, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hideho","family":"Uchiyama","sequence":"additional","affiliation":[{"name":"Department of Life and Environmental System Science, Graduate School of NanoBio Sciences, Yokohama City University, 22-2 Seto, Kanazawa-ku, Yokohama 236-0027, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masahiro","family":"Hosono","sequence":"additional","affiliation":[{"name":"Division of Cell Recognition Study, Institute of Molecular Biomembrane and Glycobiology, Tohoku Pharmaceutical University, 4-4-1 Komatsushima, Aoba-ku, Sendai 981-8558, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yukiko","family":"Ogawa","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Faculty of Pharmaceutical Science, Nagasaki International University, 2825-7 Huis Ten Bosch, Sasebo, Nagasaki 859-3298, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hideaki","family":"Fujita","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Faculty of Pharmaceutical Science, Nagasaki International University, 2825-7 Huis Ten Bosch, Sasebo, Nagasaki 859-3298, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiharu","family":"Hamako","sequence":"additional","affiliation":[{"name":"Department of Biology, School of Health Sciences, Fujita Health University, Toyoake, Aichi 470-1192, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taei","family":"Matsui","sequence":"additional","affiliation":[{"name":"Department of Biology, School of Health Sciences, Fujita Health University, Toyoake, Aichi 470-1192, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2782-6158","authenticated-orcid":false,"given":"Yasuhiro","family":"Ozeki","sequence":"additional","affiliation":[{"name":"Department of Life and Environmental System Science, Graduate School of NanoBio Sciences, Yokohama City University, 22-2 Seto, Kanazawa-ku, Yokohama 236-0027, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2015,12,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"4370","DOI":"10.3390\/md11114370","article-title":"Bivalve omics: State of the art and potential applications for the biomonitoring of harmful marine compounds","volume":"11","author":"Manfrin","year":"2013","journal-title":"Mar. 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