Abstract

Sterol regulatory element binding proteins (SREBPs) are a family of transcription factors that modulate the expression of several enzymes implicated in endogenous cholesterol, fatty acid, triacylglycerol and phospholipid synthesis. In this study evidences for SREBP-1 regulation at translational level have been reported. By several experimental approaches, we demonstrated that 5' UTR of the SREBP-1a mRNA contains an internal ribosome entry site (IRES). Transfection experiments with SREBP-1a UTR inserted in a dicistronic reporter vector showed a remarkable increase of the downstream cistron translation, through a cap-independent mechanism. Insertion of the SREBP-1c 5’ UTR in the same vector also stimulated the translation of the downstream cistron, but the observed effect can be ascribed, at least in part, to a cryptic promoter activity. Cellular stress conditions, such as serum starvation, caused in both Hep G2 and HeLa cells an increase in the level of SREBP-1 precursor and mature form, despite the overall reduction of protein synthesis, whereas mRNA levels for SREBP-1 were unaffected by serum starvation. Transfection experiments carried out with a dicistronic construct demonstrated that the cap-dependent translation was more affected than IRES-mediated translation by serum starvation. The thapsigargin- and tunicamycin-induced unfolded protein response also increased SREBP-1 expression in Hep G2 cells, through the cap-independent translation mediated by IRES. Overall, these data indicate that the presence of IRES in the SREBP-1a 5’ UTR allows translation to be maintained under conditions that are inhibitory to cap-dependent translation.

Autore Pugliese

• Damiano Fabrizio , Siculella Luisa

Tutti gli autori

• F. Damiano , S. Alemanno , G. V. Gnoni , L. Siculella

Titolo volume/Rivista

BIOCHEMICAL JOURNAL

Anno di pubblicazione

2010

ISSN

1470-8728

ISBN

Non Disponibile

Numero di citazioni Wos

34

Ultimo Aggiornamento Citazioni

28/04/2018

Numero di citazioni Scopus

35

Ultimo Aggiornamento Citazioni

28/04/2018

Settori ERC

Non Disponibile

Codici ASJC

Non Disponibile