Alternative splicing produces a constitutively active form of human SREBP-1.
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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
Alternative splicing produces a constitutively active form of human SREBP-1.
Biochem Biophys Res Commun. 2008 Apr 11;368(3):820-6. doi: 10.1016/j.bbrc.2008.02.004. Epub 2008 Feb 11.
- PubMed ID
- 18267114 [ View in PubMed]
- 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-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.