Jm. Rosenfeld et Tf. Osborne, HLH106, A DROSOPHILA STEROL REGULATORY ELEMENT-BINDING PROTEIN IN A NATURAL CHOLESTEROL AUXOTROPH, The Journal of biological chemistry, 273(26), 1998, pp. 16112-16121
In mammalian cells, sterol regulatory element-binding proteins (SREBPs
) coordinate metabolic flux through the cholesterol and fatty acid bio
synthetic pathways in response to intracellular cholesterol levels. We
describe experiments that evaluate the functional equivalence of mamm
alian SREBPs and the insect homologue of SREBP-1a, HLH106, in both mam
malian and insect cell culture systems. HLH106 binds to both palindrom
ic E-boxes and direct repeat sterol regulatory elements (SREs) efficie
ntly, suggesting that it has a dual DNA binding specificity similar to
the mammalian proteins, The amino-terminal ''mature'' protein activat
es transcription from mammalian SREs in both mammalian and Drosophila
tissue culture cells. Additionally, HLH106 also requires a ubiquitous
regulatory co-activator to efficiently activate transcription from mam
malian SREs, These properties are shared with its mammalian counterpar
ts. When expressed in mammalian cells, the carboxyl-terminal portion a
lso localizes to perinuclear membranes similar to mammalian SREBPs. Fu
rthermore, membrane-bound HLH106 is proteolytically processed in respo
nse to intracellular sterol levels in mammalian cells in an SREBP clea
vage-activating protein-stimulated fashion, The presence of an SREBP h
omologue in Drosophila whose processing is regulated by intracellular
sterol levels when expressed in mammalian cells suggests that related
processing machinery exists in insect cells. This is notable, since in
sects are reportedly incapable of de novo sterol biosynthesis.