Les protéines à domaine START, des trafiquants intracellulaires de lipides

Alpy, Fabien; Legueux, François; Bianchetti, Laurent; Tomasetto, Catherine

doi:10.1051/medsci/2009252181

Cited by 16 publications

(13 citation statements)

References 49 publications

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“…The START domains do not behave as classical ADs in the absence of VP16 (Figure 3F), and based on our site-directed mutagenesis, protein–metabolite immunoisolation experiments and structural modeling, we conclude that the likely mode of action is via ligand-binding. Since several START domain-containing proteins from humans have been found in the nucleus [8,9], our findings support a possible role for the START domain in regulating gene expression in both plants and animals.…”

Section: Discussionsupporting

confidence: 74%

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Shared functions of plant and mammalian StAR-related lipid transfer (START) domains in modulating transcription factor activity

et al. 2014

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BackgroundSteroidogenic acute regulatory protein (StAR)-related lipid transfer (START) domains were first identified from mammalian proteins that bind lipid/sterol ligands via a hydrophobic pocket. In plants, predicted START domains are predominantly found in homeodomain leucine zipper (HD-Zip) transcription factors that are master regulators of cell-type differentiation in development. Here we utilized studies of Arabidopsis in parallel with heterologous expression of START domains in yeast to investigate the hypothesis that START domains are versatile ligand-binding motifs that can modulate transcription factor activity.ResultsOur results show that deletion of the START domain from Arabidopsis Glabra2 (GL2), a representative HD-Zip transcription factor involved in differentiation of the epidermis, results in a complete loss-of-function phenotype, although the protein is correctly localized to the nucleus. Despite low sequence similarly, the mammalian START domain from StAR can functionally replace the HD-Zip-derived START domain. Embedding the START domain within a synthetic transcription factor in yeast, we found that several mammalian START domains from StAR, MLN64 and PCTP stimulated transcription factor activity, as did START domains from two Arabidopsis HD-Zip transcription factors. Mutation of ligand-binding residues within StAR START reduced this activity, consistent with the yeast assay monitoring ligand-binding. The D182L missense mutation in StAR START was shown to affect GL2 transcription factor activity in maintenance of the leaf trichome cell fate. Analysis of in vivo protein–metabolite interactions by mass spectrometry provided direct evidence for analogous lipid-binding activity in mammalian and plant START domains in the yeast system. Structural modeling predicted similar sized ligand-binding cavities of a subset of plant START domains in comparison to mammalian counterparts.ConclusionsThe START domain is required for transcription factor activity in HD-Zip proteins from plants, although it is not strictly necessary for the protein’s nuclear localization. START domains from both mammals and plants are modular in that they can bind lipid ligands to regulate transcription factor function in a yeast system. The data provide evidence for an evolutionarily conserved mechanism by which lipid metabolites can orchestrate transcription. We propose a model in which the START domain is used by both plants and mammals to regulate transcription factor activity.Electronic supplementary materialThe online version of this article (doi:10.1186/s12915-014-0070-8) contains supplementary material, which is available to authorized users.

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Section: Discussionsupporting

confidence: 74%

“…Experimental evidence for START domains as ligand-binding motifs derives largely from mammalian proteins [8,9]. The human genome encodes 15 START domain-containing proteins, several of which are implicated in disease [10].…”

Section: Introductionmentioning

confidence: 99%

Shared functions of plant and mammalian StAR-related lipid transfer (START) domains in modulating transcription factor activity

et al. 2014

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“…Besides, CBP contains a unique structural feature of START domain [8], [27] that aids in lipid recognition or transfer [28], [29]. CBP also can be isolated and purified from the cytoplasm of the silk glands of N4 strain and binds lutein with a 1∶1 molar ratio [8].…”

Section: Discussionmentioning

confidence: 99%

Combined Effect of Cameo2 and CBP on the Cellular Uptake of Lutein in the Silkworm, Bombyx mori

et al. 2014

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Formation of yellow-red color cocoons in the silkworm, Bombyx mori, occurs as the result of the selective delivery of carotenoids from the midgut to the silk gland via the hemolymph. This process of pigment transport is thought to be mediated by specific cellular carotenoids carrier proteins. Previous studies indicated that two proteins, Cameo2 and CBP, are associated with the selective transport of lutein from the midgut into the silk gland in Bombyx mori. However, the exact roles of Cameo2 and CBP during the uptake and transport of carotenoids are still unknown. In this study, we investigated the respective contributions of these two proteins to lutein and β-carotene transport in Bombyx mori as well as commercial cell-line. We found that tissues, expressed both Cameo2 and CBP, accumulate lutein. Cells, co-expressed Cameo2 and CBP, absorb 2 fold more lutein (P<0.01) than any other transfected cells, and the rate of cellular uptake of lutein was concentration-dependent and reached saturation. From immunofluorescence staining, confocal microscopy observation and western blot analysis, Cameo2 was localized at the membrane and CBP was expressed in the cytosol. What’s more, bimolecular fluorescence complementation analysis showed that these two proteins directly interacted at cellular level. Therefore, Cameo2 and CBP are necessarily expressed in midguts and silk glands for lutein uptake in Bombyx mori. Cameo2 and CBP, as the membrane protein and the cytosol protein, respectively, have the combined effect to facilitate the cellular uptake of lutein.

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“…In mammals, 15 START domain-containing proteins were identified (35). Among these proteins, steroidogenic acute regulatory protein (StAR) and metastatic lymph node 64 (MLN64) appear to be the most well-known representatives (36).…”

Section: Typical Dlc Protein Possesses Three Domains: Sam Rhogap Andmentioning

confidence: 99%

Deleted in liver cancer protein family in human malignancies (Review)

et al. 2011

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Abstract. The Deleted in Liver Cancer (DLC) protein family comprises proteins that exert their function mainly by the Rho GTPase-activating protein (GAP) domain and by regulation of the small GTPases. Since Rho GTPases are key factors in cell proliferation, polarity, cytoskeletal remodeling and migration, the aberrant function of their regulators may lead to cell transformation. One subgroup of these proteins is the DLC family. It was found that the first identified gene from this family, DLC1, is often lost in hepatocellular carcinoma and may be involved as a tumor suppressor in the liver. Subsequent studies evaluated the hypothesis that the DLC1 gene acts as a tumor suppressor, not only in liver cancer, but also in other types of cancer. Following DLC1, two other members of the DLC protein family, DLC2 and DLC3, were identified. However, limited published data are available concerning the role of these proteins in malignant transformation. This review focuses on the structure and the role of DLC1 and its relatives in physiological conditions and summarizes data published thus far regarding DLC function in the neoplastic process.

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Les protéines à domaine START, des trafiquants intracellulaires de lipides

Cited by 16 publications

References 49 publications

Shared functions of plant and mammalian StAR-related lipid transfer (START) domains in modulating transcription factor activity

Shared functions of plant and mammalian StAR-related lipid transfer (START) domains in modulating transcription factor activity

Combined Effect of Cameo2 and CBP on the Cellular Uptake of Lutein in the Silkworm, Bombyx mori

Deleted in liver cancer protein family in human malignancies (Review)

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