• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

Analysis of functional regulation of PGMRC1

Research Project

Project/Area Number 15K07011
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Functional biochemistry
Research InstitutionKeio University

Principal Investigator

Kabe Yasuaki  慶應義塾大学, 医学部(信濃町), 講師 (20397037)

Co-Investigator(Renkei-kenkyūsha) UCHIDA Tsuyoshi  北海道大学, 理学部, 准教授 (30343742)
Project Period (FY) 2015-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
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)
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.

Report

(4 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Research-status Report
  • 2015 Research-status Report
  • Research Products

    (21 results)

All 2018 2017 2016 2015 2014 Other

All Int'l Joint Research (2 results) Journal Article (15 results) (of which Int'l Joint Research: 9 results,  Peer Reviewed: 14 results,  Open Access: 14 results,  Acknowledgement Compliant: 4 results) Presentation (4 results) (of which Invited: 2 results)

  • [Int'l Joint Research] University of Bari(Italy)

    • Related Report
      2016 Research-status Report
  • [Int'l Joint Research] University of Southern California,(米国)

    • Related Report
      2016 Research-status Report
  • [Journal Article] Gold-nanofève surface-enhanced Raman spectroscopy visualizes hypotaurine as a robust anti-oxidant consumed in cancer survival2018

    • Author(s)
      Shiota M, Naya M, Yamamoto T, Hishiki T, Tani T, Takahashi H, Kubo A, Koike D, Itoh M, Ohmura M, Kabe Y, Sugiura Y, Hiraoka N, Morikawa T, Takubo K, Suina K, Nagashima H, Sampetrean O, Nagano O, Saya H, Yamazoe S, Watanabe H, Suematsu M
    • Journal Title

      Nature Communications

      Volume: 9 Issue: 1 Pages: 1561-1561

    • DOI

      10.1038/s41467-018-03899-1

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Quiescence of adult oligodendrocyte precursor cells requires thyroid hormone and hypoxia to activate Runx1.2017

    • Author(s)
      Tokumoto Y, Tamaki S, Kabe Y, Takubo K, Suematsu M
    • Journal Title

      Scientific Reports

      Volume: 7 Issue: 1 Pages: 1019-1019

    • DOI

      10.1038/s41598-017-01023-9

    • Related Report
      2017 Annual Research Report 2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [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.
    • Journal Title

      Gastroenterology

      Volume: S0016-5085 Issue: 6 Pages: 300081-300081

    • DOI

      10.1053/j.gastro.2017.01.021

    • Related Report
      2017 Annual Research Report 2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Immunohistochemistry of aldosterone synthase leads the way to the pathogenesis of primary aldosteronism2017

    • Author(s)
      Nishimoto, K., Koga, M., Seki, T., Oki, K., Gomez-Sanchez, E.P., Gomez-Sanchez, C.E., Naruse, M., Sakaguchi, T., Morita, S., Kosaka, T., Oya, M., Ogishima, T., Yasuda, M., Suematsu, M., Kabe, T., Omura, M., Nishikawa, T., Mukai, K.
    • Journal Title

      Mol. Cell. Endocrinol.

      Volume: 441 Pages: 124-133

    • DOI

      10.1016/j.mce.2016.10.014

    • Related Report
      2017 Annual Research Report 2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [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.
    • Journal Title

      Mol Cell Endocrinol.

      Volume: 441 Pages: 134-139

    • DOI

      10.1016/j.mce.2016.07.031

    • Related Report
      2017 Annual Research Report 2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] CO応答性ヘムタンパク質PGRMC1による悪性腫瘍の増殖と薬剤耐性のメカニズムの解明2017

    • Author(s)
      加部泰明、末松誠
    • Journal Title

      生化学

      Volume: 89 Pages: 88-88

    • NAID

      40021439299

    • Related Report
      2017 Annual Research Report
  • [Journal Article] Disorganized steroidogenesis in adrenocortical carcinoma, a case study2017

    • 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, C.E., Yao, T., Horie, S., Watada, H.
    • Journal Title

      Endocr. Pathol.

      Volume: 28 Issue: 1 Pages: 27-35

    • DOI

      10.1007/s12022-016-9441-8

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [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.
    • Journal Title

      Pharmacological Research

      Volume: 117 Pages: 67-71

    • DOI

      10.1016/j.phrs.2016.12.023

    • Related Report
      2017 Annual Research Report 2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Cystathionine beta-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, and Suematsu M.
    • Journal Title

      Free Radical Biology & Medicine

      Volume: 99 Pages: 333-344

    • DOI

      10.1016/j.freeradbiomed.2016.08.025

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access
  • [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.
    • Journal Title

      Int J Endocrinol.

      Volume: 2016 Pages: 7834356-7834356

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [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.
    • Journal Title

      Arthritis Res Ther.

      Volume: 18 Issue: 1 Pages: 112-112

    • DOI

      10.1186/s13075-016-1013-2

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access
  • [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.
    • Journal Title

      Nature Communications

      Volume: 7 Issue: 1 Pages: 11030-11030

    • DOI

      10.1038/ncomms11030

    • NAID

      130007529314

    • Related Report
      2016 Research-status Report 2015 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] CO-CBS-H2 S Axis: From Vascular Mediator to Cancer Regulator.2016

    • Author(s)
      Suematsu M, Nakamura T, Tokumoto Y, Yamamoto T, Kajimura M, Kabe Y.
    • Journal Title

      Microcirculation

      Volume: 23 Issue: 3 Pages: 183-190

    • DOI

      10.1111/micc.12253

    • Related Report
      2016 Research-status Report 2015 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [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
    • Journal Title

      PLoS One

      Volume: 10 Issue: 2 Pages: 1-22

    • DOI

      10.1371/journal.pone.0118662

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Impacts of CD44 knockdown in cancer cells on tumor and host metabolic systems revealed by quantitative imaging mass spectrometry.2014

    • Author(s)
      Ohmura M, Hishiki T, Yamamoto T, Nakanishi T, Kubo A, Tsuchihashi K, Tamada M, Toue S, Kabe Y, Saya H and Suematsu M
    • Journal Title

      Nitric Oxide

      Volume: pii: S1089-8603 Pages: 495-499

    • DOI

      10.1016/j.niox.2014.11.005

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] ヘム含有受容体PGRMC1の構造と機能2017

    • Author(s)
      加部泰明
    • Organizer
      第41回日本鉄バイオサイエンス学会学術集会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] 新規ガス受容体PGRMC1の構造的機能制御の解明2016

    • Author(s)
      加部泰明
    • Organizer
      第89回日本生化学会大会
    • Place of Presentation
      仙台国際センター
    • Year and Date
      2016-09-25
    • Related Report
      2016 Research-status Report
  • [Presentation] 新規ガス受容体PGRMC1の構造的機能制御の解明2016

    • Author(s)
      加部泰明
    • Organizer
      日本プロテオーム学会2016年大会
    • Place of Presentation
      北里大学白金キャンパス
    • Year and Date
      2016-07-27
    • Related Report
      2016 Research-status Report
  • [Presentation] 肝炎保護成分グリチルリチンの新規受容体探索と生理機能の解明2015

    • Author(s)
      加部泰明
    • Organizer
      第22回肝細胞研究会
    • Place of Presentation
      米子コンベンションセンター(鳥取県米子市)
    • Year and Date
      2015-06-04
    • Related Report
      2015 Research-status Report
    • Invited

URL: 

Published: 2015-04-16   Modified: 2022-02-16  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi