Alternative splicing produces a constitutively active form of human SREBP-1.
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-1Delta) contains a translational stop codon-encoding exon sequence between exons 7 and 8. It produces SREBP-1aDelta (470 a.a.) and SREBP-1cDelta (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-1aDelta and SREBP-1cDelta transactivated lipogenic gene promoters to the same extent as that induced by N-terminal active fragments of SREBP-1a and SREBP-1c, respectively. SREBP-1Delta 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-1Delta expression to total SREBP-1 expression in HepG2 cells was not affected by either insulin or high glucose treatment.
Harada
Nagakatsu
N
Department of Nutrition and Metabolism, Institute of Health Biosciences, University of Tokushima Graduate School, 3-18-15, Kuramoto-cho, Tokushima City 770-8503, Japan.
Yonemoto
Haruka
H
Yoshida
Masaki
M
Yamamoto
Hironori
H
Yin
Yunjie
Y
Miyamoto
Aiko
A
Hattori
Atsushi
A
Wu
Qishisan
Q
Nakagawa
Tadahiko
T
Nakano
Masayuki
M
Teshigawara
Kiyoshi
K
Mawatari
Kazuaki
K
Hosaka
Toshio
T
Takahashi
Akira
A
Nakaya
Yutaka
Y
D000273:Adipose Tissue / Q000378:metabolism*; D017398:Alternative Splicing / Q000235:genetics*; D002460:Cell Line; D006801:Humans; D008099:Liver / Q000378:metabolism*; D009928:Organ Specificity; D020033:Protein Isoforms / Q000235:genetics; D022821:RNA Splice Sites / Q000235:genetics*; D051780:Sterol Regulatory Element Binding Protein 1 / Q000235:genetics* / Q000378:metabolism*; D014018:Tissue Distribution
D020033:Protein Isoforms; D022821:RNA Splice Sites; C497387:SREBF1 protein, human; D051780:Sterol Regulatory Element Binding Protein 1