Proteolytic activation of SREBPs during adipocyte differentiation

Jun Inoue, Hidetoshi Kumagai, Tomoyuki Terada, Masatomo Maeda, Makoto Shimizu, Ryuichiro Sato

Research output: Contribution to journalArticle

25 Scopus citations

Abstract

A member of sterol regulatory element-binding protein (SREBP) family, SREBP-1, is a key regulator of adipocyte differentiation. Expression of the SREBP-1 gene is induced during adipocyte differentiation, but proteolytic activation of the synthesized precursor form of SREBP-1 has not been well analyzed. The proteolytic processing of SREBPs is severely suppressed in sterol loaded culture cells. Here we report that a splicing isoform, SREBP-1a, is predominantly expressed in 3T3-L1 preadipocytes and adipocytes, and that the nuclear active form of SREBP-1 protein increases in adipocyte differentiation. We further show that the amount of nuclear SREBP-2 protein also increases despite no increase in SREBP-2 mRNA, suggesting that proteolytic cleavage of SREBPs is induced in lipid loaded adipocytes. Northern blot analyses reveal that mRNA levels for SREBP cleavage-activating protein (SCAP), Site-1 protease (S1P), and Site-2 protease (S2P), which participate in the proteolytic processing of SREBPs, are relatively unaffected in adipogenesis. These results demonstrate that SREBP-2 appears to promote adipocyte differentiation as well as SREBP-1 and that the proteolytic activation of SREBPs may be induced by an as-yet unidentified mechanism in lipid loaded adipocytes.

Original languageEnglish (US)
Pages (from-to)1157-1161
Number of pages5
JournalBiochemical and Biophysical Research Communications
Volume283
Issue number5
DOIs
StatePublished - 2001

Keywords

  • 3T3-L1 cells
  • Adipogenesis
  • SREBP

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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