Alternative splicing produces a constitutively active form of human SREBP-1

Nagakatsu Harada, Haruka Yonemoto, Masaki Yoshida, Hironori Yamamoto, Yunjie Yin, Aiko Miyamoto, Atsushi Hattori, Qishisan Wu, Tadahiko Nakagawa, Masayuki Nakano, Kiyoshi Teshigawara, Kazuaki Mawatari, Toshio Hosaka, Akira Takahashi, Yutaka Nakaya

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

We identified a novel alternative splicing event that constitutively produces a truncated active form of human sterol regulatory element-binding protein 1 (SREBP-1). A cDNA of this splicing variant (named SREBP-1Δ) contains a translational stop codon-encoding exon sequence between exons 7 and 8. It produces SREBP-1aΔ (470 a.a.) and SREBP-1cΔ (446 a.a.) proteins that lack transmembrane and C-terminal regulatory sequences necessary for localization of SREBP-1 to the endoplasmic reticulum. A luciferase reporter assay showed that SREBP-1aΔ and SREBP-1cΔ transactivated lipogenic gene promoters to the same extent as that induced by N-terminal active fragments of SREBP-1a and SREBP-1c, respectively. SREBP-1Δ mRNA is expressed in human cell lines as well as adipose and liver tissues. Expression levels ranged from 5% to 16% of total SREBP-1 expression. The ratio of SREBP-1Δ expression to total SREBP-1 expression in HepG2 cells was not affected by either insulin or high glucose treatment.

Original languageEnglish
Pages (from-to)820-826
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume368
Issue number3
DOIs
Publication statusPublished - Apr 11 2008
Externally publishedYes

    Fingerprint

Keywords

  • Alternative splicing
  • High glucose
  • Insulin
  • Promoter activity
  • Sterol regulatory element-binding protein

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

Cite this

Harada, N., Yonemoto, H., Yoshida, M., Yamamoto, H., Yin, Y., Miyamoto, A., Hattori, A., Wu, Q., Nakagawa, T., Nakano, M., Teshigawara, K., Mawatari, K., Hosaka, T., Takahashi, A., & Nakaya, Y. (2008). Alternative splicing produces a constitutively active form of human SREBP-1. Biochemical and Biophysical Research Communications, 368(3), 820-826. https://doi.org/10.1016/j.bbrc.2008.02.004