Analysis of functional regulation of PGMRC1
Project/Area Number |
15K07011
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Functional biochemistry
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Research Institution | Keio University |
Principal Investigator |
Kabe Yasuaki 慶應義塾大学, 医学部(信濃町), 講師 (20397037)
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Co-Investigator(Renkei-kenkyūsha) |
UCHIDA Tsuyoshi 北海道大学, 理学部, 准教授 (30343742)
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Project Period (FY) |
2015-04-01 – 2018-03-31
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Project Status |
Completed (Fiscal Year 2017)
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Budget Amount *help |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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Keywords | ヘム / がん増殖 / 構造生物科学 / 金属タンパク質 / 結晶構造解析 / 癌 |
Outline of Final Research Achievements |
Progesterone receptor membrane component 1 (PGRMC1) is a haem-containing protein that interacts with epidermal growth factor receptor (EGFR) and cytochromes P450 to regulate cancer proliferation and chemoresistance; its structural basis remains unknown. Crystallographic analyses revealed that PGRMC1 forms a stable dimer through stacking interactions of two protruding haem molecules. The haem iron is five-coordinated by Tyr113. Haem-mediated PGRMC1 dimerization is required for interactions with EGFR and cytochromes P450, cancer proliferation and chemoresistance against anti-cancer drugs. This study demonstrates protein dimerization via haem-haem stacking, which has not been seen in eukaryotes, and provides insights into its functional significance in cancer.
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Report
(4 results)
Research Products
(28 results)
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[Journal Article] Stearoyl-CoA Desaturase Promotes Liver Fibrosis and Tumor Development in Mice via a Wnt Positive-Signaling Loop by Stabilization of Low-Density Lipoprotein-Receptor-Related Proteins 5 and 6.2017
Author(s)
Lai KK, Kweon SM, Chi F, Hwang E, Kabe Y, Higashiyama R, Qin L, Yan R, Wu RP, Fujii N, French S, Xu J, Wang JY, Murali R, Mishra L, Lee JS, Ntambi JM, Tsukamoto H.
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Journal Title
Gastroenterology
Volume: S0016-5085
Pages: 300081
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Somatic KCNJ5 mutation occurring early in adrenal development may cause a novel form of juvenile primary aldosteronism.2017
Author(s)
Tamura A, Nishimoto K, Seki T, Matsuzawa Y, Saito J, Omura M, Gomez-Sanchez CE, Makita K, Matsui S, Moriya N, Inoue A, Nagata M, Sasano H, Nakamura Y, Yamazaki Y, Kabe Y, Mukai K, Kosaka T, Oya M, Suematsu S, Nishikawa T.
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Journal Title
Mol Cell Endocrinol.
Volume: 441
Pages: 134-139
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Sigma-2 receptor and progesterone receptor membrane component 1 (PGRMC1) are two different proteins: Proofs by fluorescent labeling and binding of sigma-2 receptor ligands to PGRMC1.2016
Author(s)
Pati ML, Groza D, Riganti C, Kopecka J, Niso M, Berardi F, Hager S, Heffeter P, Hirai M, Tsugawa H, Kabe Y, Suematsu M, Abate C.
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Journal Title
Pharmacological Research
Volume: 117
Pages: 67-71
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
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[Journal Article] Immunohistochemistry of aldosterone synthase leads the way to the pathogenesis of primary aldosteronism.2016
Author(s)
Nishimoto K, Koga M, Seki T, Oki K, Gomez-Sanchez EP, Gomez-Sanchez CE, Naruse M, Sakaguchi T, Morita S, Kosaka T, Oya M, Ogishima T, Yasuda M, Suematsu M, Kabe Y, Omura M, Nishikawa T, Mukai K.
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Journal Title
Mol Cell Endocrinol.
Volume: 441
Pages: 124-133
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Cystathionine β-synthase and PGRMC1 as CO sensors.2016
Author(s)
Kabe Y, Yamamoto T, Kajimura M, Sugiura Y, Koike I, Ohmura M, Nakamura T, Tokumoto Y, Tsugawa H, Handa H, Kobayashi T, Suematsu M.
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Journal Title
Free Radic Biol Med.
Volume: 99
Pages: 333-344
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] Human Adrenocortical Remodeling Leading to Aldosterone-Producing Cell Cluster Generation.2016
Author(s)
Nishimoto K, Seki T, Hayashi Y, Mikami S, Al-Eyd G, Nakagawa K, Morita S, Kosaka T, Oya M, Mitani F, Suematsu M, Kabe Y, Mukai K.
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Journal Title
Int J Endocrinol.
Volume: 2016
Pages: 7834356
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Disorganized Steroidogenesis in Adrenocortical Carcinoma, a Case Study.2016
Author(s)
Uchida T, Nishimoto K, Fukumura Y, Asahina M, Goto H, Kawano Y, Shimizu F, Tsujimura A, Seki T, Mukai K, Kabe Y, Suematsu M, Gomez-Sanchez CE, Yao T, Horie S, Watada H.
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Journal Title
Endocr Pathol.
Volume: 28
Pages: 27-35
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Alteration of matrix metalloproteinase-3 O-glycan structure as a biomarker for disease activity of rheumatoid arthritis.2016
Author(s)
Takeshita M, Kuno A, Suzuki K, Matsuda A, Shimazaki H, Nakagawa T, Otomo Y, Kabe Y, Suematsu M, Narimatsu H, Takeuchi T.
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Journal Title
Arthritis Res Ther.
Volume: 18
Pages: 112
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Haem-dependent dimerization of PGRMC1/Sigma-2 receptor facilitates cancer proliferation and chemoresistance.2016
Author(s)
Kabe Y, Nakane T, Koike I, Yamamoto T, Sugiura Y, Harada E, Sugase K, Shimamura T, Ohmura M, Muraoka K, Yamamoto A, Uchida T, Iwata S, Yamaguchi Y, Krayukhina E, Noda M, Handa H, Ishimori K, Uchiyama S, Kobayashi T, Suematsu M.
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Journal Title
Nat Commun.
Volume: 7
Pages: 11030
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] Haem-dependent dimerization of PGRMC1/Sigma-2 receptor facilitates cancer proliferation and chemoresistance.2016
Author(s)
Kabe Y, Nakane T, Koike I, Yamamoto T, Sugiura Y, Harada E, Sugase K, Shimamura T, Ohmura M, Muraoka K, Yamamoto A, Uchida T, Iwata S, Yamaguchi Y, Krayukhina E, Noda M, Handa H, Ishimori K, Uchiyama S, Kobayashi T, Suematsu M.
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Journal Title
Nature Communications
Volume: 7
Pages: 11030
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] LATS1 and LATS2 phosphorylate CDC26 to modulate assembly of the tetratricopeptide repeat subcomplex of APC/C.2015
Author(s)
Masuda K, Chiyoda T, Sugiyama N, Segura-Cabrera A, Kabe Y, Ueki A, Banno K, Suematsu M, Aoki D, Ishihama Y, Saya H, Kuninaka S.
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Journal Title
PLos One
Volume: 10
Pages: e0118662
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Impacts of CD44 knockdown in cancer cells on tumor and host metabolic systems revealed by quantitative imaging mass spectrometry.2015
Author(s)
Ohmura M, Hishiki T, Yamamoto T, Nakanishi T, Kubo A, Tsuchihashi K, Tamada M, Toue S, Kabe Y, Saya H, Suematsu M.
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Journal Title
Nitric Oxide
Volume: 46
Pages: 102-113
DOI
Related Report
Peer Reviewed
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