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

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.

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.

Biochem. Biophys. Res. Commun. 368:820-826(2008) [PubMed] [Europe PMC]

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