Cell surface expression of CD147/EMMPRIN is regulated by cyclophilin 60

Tatiana Pushkarsky, Vyacheslav Yurchenko, Christophe Vanpouille, Beda Brichacek, Iosif Vaisman, Shigetsugu Hatakeyama, Keiichi I. Nakayama, Barbara Sherry, Michael I. Bukrinsky

Research output: Contribution to journalArticle

61 Citations (Scopus)

Abstract

CD147, also known as extracellular matrix metalloproteinase inducer, is a regulator of matrix metalloproteinase production and also serves as a signaling receptor for extracellular cyclophilins. Previously, we demonstrated that cell surface expression of CD147 is sensitive to cyclophilin-binding drug cyclosporin A, suggesting involvement of a cyclophilin in the regulation of intracellular transport of CD147. In this report, we identify this cyclophilin as cyclophilin 60 (Cyp60), a distinct member of the cyclophilin family of proteins. CD147 co-immunoprecipitated with Cyp60, and confocal immunofluorescent microscopy revealed intracellular colocalization of Cyp60 and CD147. This interaction with Cyp60 involved proline 211 of CD147, which was shown previously to be critical for interaction between CD147 and another cyclophilin, cyclophilin A, in solution. Mutation of this proline residue abrogated co-immunoprecipitation of CD147 and Cyp60 and reduced surface expression of CD147 on the plasma membrane. Suppression of Cyp60 expression using RNA interference had an effect similar to that of cyclosporin A: reduction of cell surface expression of CD147. These results suggest that Cyp60 plays an important role in the translocation of CD147 to the cell surface. Therefore, Cyp60 may present a novel target for therapeutic interventions in diseases where CD147 functions as a pathogenic factor, such as cancer, human immunodeficiency virus infection, or rheumatoid arthritis.

Original languageEnglish
Pages (from-to)27866-27871
Number of pages6
JournalJournal of Biological Chemistry
Volume280
Issue number30
DOIs
Publication statusPublished - Jul 29 2005

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Fingerprint Dive into the research topics of 'Cell surface expression of CD147/EMMPRIN is regulated by cyclophilin 60'. Together they form a unique fingerprint.

  • Cite this

    Pushkarsky, T., Yurchenko, V., Vanpouille, C., Brichacek, B., Vaisman, I., Hatakeyama, S., Nakayama, K. I., Sherry, B., & Bukrinsky, M. I. (2005). Cell surface expression of CD147/EMMPRIN is regulated by cyclophilin 60. Journal of Biological Chemistry, 280(30), 27866-27871. https://doi.org/10.1074/jbc.M503770200