Proinsulin C-peptide regulates ribosomal RNA expression

Emma Lindahl, Ulrika Nyman, Farasat Zaman, Carina Palmberg, Anna Cascante, Jawed Shafqat, Masaharu Takigawa, Lars Sävendahl, Hans Jörnvall, Bertrand Joseph

Research output: Contribution to journalArticle

38 Citations (Scopus)

Abstract

Proinsulin C-peptide is internalized into cells, but a function of its intracellular localization has not been established. We now demonstrate that, upon cellular entry, C-peptide is localized to the nucleoli, where it promotes transcription of genes encoding for ribosomal RNA. We find that C-peptide binds to histones and enhances acetylation of lysine residue 16 of histone H4 at the promoter region of genes for ribosomal RNA. In agreement with synchrony of ribosomal RNA synthesis and cell proliferation, we show that C-peptide stimulates proliferation in chondrocytes and HEK-293 cells. This regulation of ribosomal RNA provides a mechanism by which C-peptide can exert transcriptional effects and implies that the peptide has growth factor activity.

Original languageEnglish
Pages (from-to)3462-3469
Number of pages8
JournalJournal of Biological Chemistry
Volume285
Issue number5
DOIs
Publication statusPublished - Jan 29 2010

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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    Lindahl, E., Nyman, U., Zaman, F., Palmberg, C., Cascante, A., Shafqat, J., Takigawa, M., Sävendahl, L., Jörnvall, H., & Joseph, B. (2010). Proinsulin C-peptide regulates ribosomal RNA expression. Journal of Biological Chemistry, 285(5), 3462-3469. https://doi.org/10.1074/jbc.M109.053587