StarD10, a START Domain Protein Overexpressed in Breast Cancer, Functions as a Phospholipid Transfer Protein

Olayioye, Monilola A.; Vehring, Stefanie; Müller, Peter; Herrmann, Andreas; Schiller, Jürgen; Thiele, Christoph; Lindeman, Geoffrey J.; Visvader, Jane E.; Pomorski, Thomas

doi:10.1074/jbc.m413330200

Cited by 84 publications

(80 citation statements)

References 41 publications

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“…Si STARD2, STARD7 et STARD10 sont des protéines composées uniquement d'un domaine START, STARD11 possède deux autres domaines fonctionnels d'interaction avec les membranes, un domaine PH (pleckstrin homology) et un motif FFAT (two phenylalanine in an acidic tract) ainsi qu'un domaine potentiel coiled-coil et deux motifs riches en sérines [13]. STARD2 et D10 lient toutes deux la phosphatidylcholine (PC) et STARD10 lie également la phosphatidyléthanolamine (PE) [14,15]. Il est vraisemblable que STARD7 lie les phospholipides.…”

Section: Le Groupe Des Autres Transporteurs De Stérolsunclassified

Les protéines à domaine START, des trafiquants intracellulaires de lipides

et al. 2009

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Section: Le Groupe Des Autres Transporteurs De Stérolsunclassified

Les protéines à domaine START, des trafiquants intracellulaires de lipides

et al. 2009

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“…In vivo, PC and PE are recovered by immunoprecipitation of overexpressed STARD10 in HEK-293 cells. In both the in vitro and in vivo studies, PC appears to be the preferred lipid for STARD10 (Olayioye et al 2005). Phosphorylation of STARD10 on Ser284 by casein kinase II decreases in vitro lipid transport activity, possibly by decreasing membrane association (Olayioye et al 2007).…”

Section: Stard2/pctp Subfamily: the Phosphatidylcholine And Ceramide mentioning

confidence: 94%

“…In liver mitochondria, cholesterol is hydroxylated on the side chain at position C27 or C25 by the cytochrome P450 enzyme CYP27A1 to produce the oxysterols 27-hydroxycholesterol (27HC) or 25-hydroxycholesterol (25HC) (Li et al 2007). In addition to simply serving as intermediates in bile acid biosynthetic pathway, 27HC and 25HC are cellular signals (Tsujishita & Hurley 2000, Roderick et al 2002, Olayioye et al 2005, Murcia et al 2006, Bose et al 2008a,b, Kudo et al 2008, Rodriguez-Agudo et al 2008, Barbar et al 2009, Horibata & Sugimoto 2010, Thorsell et al 2011 (Kirkby et al 2010).…”

Section: Cholesterol Trafficking and Homeostasismentioning

confidence: 99%

“…Recombinant purified STARD10 specifically extracts PC and PE from reconstituted lipid vesicles and enhances PC and PE transfer from donor to acceptor vesicles in vitro (Olayioye et al 2005). In vivo, PC and PE are recovered by immunoprecipitation of overexpressed STARD10 in HEK-293 cells.…”

Section: Stard2/pctp Subfamily: the Phosphatidylcholine And Ceramide mentioning

confidence: 99%

“…Unexpectedly, loss of STARD10 expression was found to be an independent marker for poor patient outcome and may be used to identify a specific subgroup of patients at high risk (Murphy et al 2009). Whether the beneficial effect for STARD10 expression in breast cancer is related to its PC binding/transport activity will require elucidating the biological functions of STARD10 in mammary tissues (Olayioye et al 2005). This function most likely will be related to the phosphorylation state of STARD10, therefore elucidating the phosphatase(s) responsible for the dephosphorylation and activation of STARD10, and the pathways involved in STARD10 activation are important future studies (Olayioye et al 2007).…”

Section: Stard7: a Phosphatidylcholine-binding Proteinmentioning

confidence: 99%

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The mammalian START domain protein family in lipid transport in health and disease

Clark¹

2011

Journal of Endocrinology

135

109

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Lipid transfer proteins of the steroidogenic acute regulatory protein-related lipid transfer (START) domain family are defined by the presence of a conserved w210 amino acid sequence that folds into an a/b helix-grip structure forming a hydrophobic pocket for ligand binding. The mammalian START proteins bind diverse ligands, such as cholesterol, oxysterols, phospholipids, sphingolipids, and possibly fatty acids, and have putative roles in non-vesicular lipid transport, thioesterase enzymatic activity, and tumor suppression. However, the biological functions of many members of the START domain protein family are not well established. Recent research has focused on characterizing the cell-type distribution and regulation of the START proteins, examining the specificity and directionality of lipid transport, and identifying disease states associated with dysregulation of START protein expression. This review summarizes the current concepts of the proposed physiological and pathological roles for the mammalian START domain proteins in cholesterol and lipid trafficking.

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Genetic ablation or chemical inhibition of phosphatidylcholine transfer protein attenuates diet-induced hepatic glucose production

et al. 2011

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Phosphatidylcholine transfer protein (PC-TP, synonym StARD2) is a highly specific intracellular lipid binding protein that is enriched in liver. Coding region polymorphisms in both humans and mice appear to confer protection against measures of insulin resistance. The current study was designed to test the hypotheses that Pctp−/− mice are protected against diet-induced increases in hepatic glucose production and that small molecule inhibition of PC-TP recapitulates this phenotype. Pctp−/− and wild type mice were subjected to high fat feeding, and rates of hepatic glucose production and glucose clearance were quantified by hyperinsulinemic euglycemic clamp studies and pyruvate tolerance tests. These studies revealed that high fat diet-induced increases in hepatic glucose production were markedly attenuated in Pctp−/− mice. Small molecule inhibitors of PC-TP were synthesized and their potencies, as well as mechanism of inhibition, were characterized in vitro. An optimized inhibitor was administered to high fat fed mice and used to explore effects on insulin signaling in cell culture systems. Small molecule inhibitors bound PC-TP, displaced phosphatidylcholines from the lipid binding site and increased the thermal stability of the protein. Administration of the optimized inhibitor to wild type mice attenuated hepatic glucose production associated with high fat feeding, but had no activity in Pctp−/− mice. Indicative of a mechanism for reducing glucose intolerance that is distinct from commonly utilized insulin-sensitizing agents, the inhibitor promoted insulin-independent phosphorylation of key insulin signaling molecules. These findings suggest PC-TP inhibition as a novel therapeutic strategy in the management of hepatic insulin resistance.

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StarD10, a START Domain Protein Overexpressed in Breast Cancer, Functions as a Phospholipid Transfer Protein

Cited by 84 publications

References 41 publications

Les protéines à domaine START, des trafiquants intracellulaires de lipides

Les protéines à domaine START, des trafiquants intracellulaires de lipides

The mammalian START domain protein family in lipid transport in health and disease

Genetic ablation or chemical inhibition of phosphatidylcholine transfer protein attenuates diet-induced hepatic glucose production

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