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Functional analysis of human profilaggrin C-terminus region: Identification of molecular mechanism in profilaggrin processing

Research Project

Project/Area Number 24890082
Research Category

Grant-in-Aid for Research Activity Start-up

Allocation TypeSingle-year Grants
Research Field Dermatology
Research InstitutionHamamatsu University School of Medicine

Principal Investigator

SAKABE Jun-ichi  浜松医科大学, 医学部, 助教 (30631494)

Project Period (FY) 2012-08-31 – 2014-03-31
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
Fiscal Year 2013: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2012: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
KeywordsC末端領域の機能 / C末端領域結合タンパク / 蛋白のプロセシング / 表皮バリア機能 / フィラグリン / タンパク精製
Research Abstract

Filaggrin monomers are produced through profilaggrin (FLG) processing, and they are considered to be crucial in epidermal barrier function. Recently, lack of FLG C-terminus region in filaggrin gene mutation carriers was shown to be associated with significant reduction in filaggrin monomer production. To this end, we sought to evaluate the function of FLG C-terminus region in FLG processing. 1) Three types of C-terminus expression vectors were constructed, and these constructs were transfected to COS-7 cells followed by RT-PCR and Western blot analysis. 2) By pull-down assay using FLG C-terminus protein, molecules with interacting potential were searched. As result, 1) deletion of FLG C-terminus region did not alter the FLG mRNA/protein expression, suggesting that FLG C-terminus region is possibly involved in the processing of FLG, and not with the production of FLG itself. 2) Candidate proteins that interact with FLG C-terminus region were identified, such as galectin-7, etc.

Report

(3 results)
  • 2013 Annual Research Report   Final Research Report ( PDF )
  • 2012 Annual Research Report
  • Research Products

    (12 results)

All 2013 2012 2011

All Journal Article (8 results) (of which Peer Reviewed: 8 results) Presentation (4 results)

  • [Journal Article] Kallikrein-related peptidase 5 functions in proteolytic processing of profilaggrin in cultured human keratinocytes2013

    • Author(s)
      Sakabe J, Yamamoto M, Hirakawa S, Motoyama A, Ohta I, Tatsuno K, Ito T, Kabashima K, Hibino T, Tokura Y
    • Journal Title

      J Biol Chem

      Volume: 288 Pages: 17179-17189

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Kallikrein-related peptidase 5 functions in proteolytic processing of profilaggrin in cultured human keratinocytes.2013

    • Author(s)
      Sakabe J, Yamamoto M, Hirakawa S, Motoyama A, Ohta I, Tatsuno K, Ito T, Kabashima K, Hibino T, Tokura Y
    • Journal Title

      The Journal of Biological Chemistry

      Volume: 288 Pages: 17179-17189

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Topical simvastatin accelerates wound healing in diabetes by enhancing angiogenesis and lymphangiogenesis2012

    • Author(s)
      Jun Asai
    • Journal Title

      The American Journal of Pathology

      Volume: 181 Issue: 6 Pages: 2217-2224

    • DOI

      10.1016/j.ajpath.2012.08.023

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Identification of mutations in the prostaglandin transporter gene SLCO2A1 and its phenotype-genotype correlation in Japanese patients with pachydermoperiostosis.2012

    • Author(s)
      Sasaki Takashi
    • Journal Title

      Journal of Dermatological Science

      Volume: 68 Issue: 1 Pages: 36-44

    • DOI

      10.1016/j.jdermsci.2012.07.008

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A group of atopic dermatitis without IgE elevation or barrier impairment shows a high Th1 frequency: Possible immunological state of the intrinsic type2012

    • Author(s)
      Kabashima-Kubo R, Nakamura M, Sakabe, J, Sigita K, Hino R, Mori T, Kobayashi M, Bito T, Kabashima K, Ogasawara K, Nomura Y, Nomura T, Akiyama M, Shimizu H, Tokura Y.
    • Journal Title

      J Dermatol Sci

      Volume: 67 Issue: 1 Pages: 37-43

    • DOI

      10.1016/j.jdermsci.2012.04.004

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Photosensitive drug eruption induced by bicalutamide within the UVB action spectrum.2012

    • Author(s)
      Sasada Kumiko
    • Journal Title

      European Journal of Dermatology

      Volume: 22 Issue: 3 Pages: 402-403

    • DOI

      10.1684/ejd.2012.1719

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Connexin 26 (GJB2) mutations in keratitis-ichthyosisdeafness (KID) syndrome presenting with squamous cell carcinoma2012

    • Author(s)
      Sakabe J-I, Yoshiki R, Sugita K, Haruyama S, Sawada Y, Kabashima R, Bito T, Nakamura M, Tokura Y
    • Journal Title

      J Dermatol

      Volume: (in press) Issue: 9 Pages: 814-815

    • DOI

      10.1111/j.1346-8138.2011.01414.x

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Sebaceous carcinoma arising at a chronic candidiasis skin lesion of apatient with keratitis-ichthyosis-deafness (KID) syndrome2011

    • Author(s)
      Kaku Y, Tanizaki H, Tanioka M, Sakabe J, Miyagawa-Hayashino A, Tokura Y, Miyachi Y, Kabashima K
    • Journal Title

      Br J Dermatol

      Volume: 166 Issue: 1 Pages: 222-224

    • DOI

      10.1111/j.1365-2133.2011.10521.x

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Presentation] Involvement of kallikrein-related peptidase 5 in profilaggrin processing2013

    • Author(s)
      Sakabe J, Yamamoto M, Motoyama A, Ohta I, Hirakawa S, Hibino T, Tokura Y
    • Organizer
      International Investigative Dermatology (IID) 2013
    • Place of Presentation
      Edinburgh
    • Related Report
      2013 Final Research Report
  • [Presentation] Involvement of kallikrein-related peptidase 5 in profilaggrin processing.2013

    • Author(s)
      Jun-ichi Sakabe, Mami Yamamoto, Akira Motoyama, Isao Ohta, Satoshi Hirakawa, Toshihiko Hibino, Yoshiki Tokura
    • Organizer
      International Investigative Dermatology (IID) 2013
    • Place of Presentation
      Edinburgh
    • Related Report
      2013 Annual Research Report
  • [Presentation] Co-localization of kallikrein5 and profilaggrin in keratohyalin granules and reduction of filaggrin monomers by kallikrein5 downmodulation.2012

    • Author(s)
      Sakabe Jun-ichi
    • Organizer
      The 37th Annual Meeting of the Japan Society for Investigative Dermatology (JSID)
    • Place of Presentation
      Naha
    • Related Report
      2012 Annual Research Report
  • [Presentation] Mandatory role of kallikrein 5 in profilaggrin maturation and possible association of its impairment with atopic dermatitis.2012

    • Author(s)
      Sakabe Jun-ichi
    • Organizer
      The 12th Kyungpook-Hamamatsu Joint Medical Symposium Hamamatsu Meeting
    • Place of Presentation
      Hamamatsu
    • Related Report
      2012 Annual Research Report

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Published: 2012-11-27   Modified: 2019-07-29  

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