The OSBP-related protein family in humans.

Oxysterols are oxygenated derivatives of cholesterol that have a number of biological effects and play a key role in the maintenance of the body cholesterol balance. In this study, we describe the cDNA sequences and genomic structures of the recently identified human oxysterol-binding protein (OSBP)-related protein (ORP) family (Laitinen, S. et al. 1999. J. Lipid Res. 40: 2204-2211). The family now includes 12 genes/proteins, which can be divided into six distinct subfamilies. The ORP have two major structural features: a highly conserved OSBP-type sterol-binding domain in the C-terminal half and a pleckstrin homology domain present in the N-terminal region of most family members. Several ORP genes are present in S. cerevisiae, D. melanogaster, and C. elegans, suggesting that the protein family has functions of fundamental importance in the eukaryotic kingdom. Analysis of ORP mRNA levels in unloaded or acetylated LDL-loaded human macrophages revealed that the expression of ORP genes was not significantly affected by the loading, with the exception of ORP6, which was up-regulated 2-fold. The present study summarizes the basic characteristics of the OSBP-related gene/protein family in humans, and provides tools for functional analysis of the encoded proteins.

[1]  Roland Somogyi,et al.  Large Scale Gene Expression Analysis of Cholesterol-loaded Macrophages* , 2000, The Journal of Biological Chemistry.

[2]  D. Mangelsdorf,et al.  Role of LXRs in control of lipogenesis. , 2000, Genes & development.

[3]  Jean-Marc A. Lobaccaro,et al.  Regulation of mouse sterol regulatory element-binding protein-1c gene (SREBP-1c) by oxysterol receptors, LXRα and LXRβ , 2000 .

[4]  P. Edwards,et al.  Control of cellular cholesterol efflux by the nuclear oxysterol receptor LXR alpha. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[5]  F. Hegardt,et al.  Contribution of steroidogenic factor 1 to the regulation of cholesterol synthesis. , 2000, The Biochemical journal.

[6]  D. Mangelsdorf,et al.  Regulation of absorption and ABC1-mediated efflux of cholesterol by RXR heterodimers. , 2000, Science.

[7]  M. Lemmon,et al.  Signal-dependent membrane targeting by pleckstrin homology (PH) domains. , 2000, The Biochemical journal.

[8]  D. Mangelsdorf,et al.  Human White/Murine ABC8 mRNA Levels Are Highly Induced in Lipid-loaded Macrophages , 2000, The Journal of Biological Chemistry.

[9]  A. Tall,et al.  Sterol upregulation of human CETP expression in vitro and in transgenic mice by an LXR element. , 2000, The Journal of clinical investigation.

[10]  E. Ikonen,et al.  Family of human oxysterol binding protein (OSBP) homologues. A novel member implicated in brain sterol metabolism. , 1999, Journal of lipid research.

[11]  S. Kohlwein,et al.  Deletion of six open reading frames from the left arm of chromosome IV of Saccharomyces cerevisiae , 1999, Yeast.

[12]  S. Smerdon,et al.  The ankyrin repeat: a diversity of interactions on a common structural framework. , 1999, Trends in biochemical sciences.

[13]  L. Ronco,et al.  Identification of a gene encoding a human oxysterol-binding protein-homologue: a potential general molecular marker for blood dissemination of solid tumors. , 1999, Cancer research.

[14]  D. Kelly,et al.  Systematic analysis of yeast strains with possible defects in lipid metabolism , 1999, Yeast.

[15]  Andrew J. Brown,et al.  Oxysterols and atherosclerosis. , 1999, Atherosclerosis.

[16]  N. Ridgway,et al.  Differential Effects of Sphingomyelin Hydrolysis and Cholesterol Transport on Oxysterol-binding Protein Phosphorylation and Golgi Localization* , 1998, The Journal of Biological Chemistry.

[17]  N. Ridgway,et al.  Cholesterol regulates oxysterol binding protein (OSBP) phosphorylation and Golgi localization in Chinese hamster ovary cells: correlation with stimulation of sphingomyelin synthesis by 25-hydroxycholesterol. , 1998, The Biochemical journal.

[18]  B. Staels,et al.  Activation of Proliferator-activated Receptors α and γ Induces Apoptosis of Human Monocyte-derived Macrophages* , 1998, The Journal of Biological Chemistry.

[19]  S. Munro,et al.  The pleckstrin homology domain of oxysterol-binding protein recognises a determinant specific to Golgi membranes , 1998, Current Biology.

[20]  R. Hammer,et al.  Cholesterol and Bile Acid Metabolism Are Impaired in Mice Lacking the Nuclear Oxysterol Receptor LXRα , 1998, Cell.

[21]  J. Jiménez,et al.  A Drosophila homologue of oxysterol binding protein (OSBP)--implications for the role of OSBP. , 1998, Biochimica et biophysica acta.

[22]  D. Lütjohann,et al.  Importance of a Novel Oxidative Mechanism for Elimination of Brain Cholesterol , 1997, The Journal of Biological Chemistry.

[23]  I. Björkhem,et al.  Elimination of Cholesterol in Macrophages and Endothelial Cells by the Sterol 27-Hydroxylase Mechanism , 1997, The Journal of Biological Chemistry.

[24]  N. Ridgway,et al.  Altered regulation of cholesterol and cholesteryl ester synthesis in Chinese-hamster ovary cells overexpressing the oxysterol-binding protein is dependent on the pleckstrin homology domain. , 1997, The Biochemical journal.

[25]  D. Mangelsdorf,et al.  Activation of the orphan nuclear receptor steroidogenic factor 1 by oxysterols. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[26]  Timothy M. Willson,et al.  Activation of the Nuclear Receptor LXR by Oxysterols Defines a New Hormone Response Pathway* , 1997, The Journal of Biological Chemistry.

[27]  M. Fang,et al.  Kes1p shares homology with human oxysterol binding protein and participates in a novel regulatory pathway for yeast Golgi‐derived transport vesicle biogenesis. , 1996, The EMBO journal.

[28]  D. Mangelsdorf,et al.  An oxysterol signalling pathway mediated by the nuclear receptor LXRα , 1996, Nature.

[29]  D. Lütjohann,et al.  Cholesterol homeostasis in human brain: evidence for an age-dependent flux of 24S-hydroxycholesterol from the brain into the circulation. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[30]  M. Kiriakidou,et al.  Steroidogenic factor 1-dependent promoter activity of the human steroidogenic acute regulatory protein (StAR) gene. , 1996, Biochemistry.

[31]  A. Rogol,et al.  Role of steroidogenic acute regulatory protein in adrenal and gonadal steroidogenesis. , 1995, Science.

[32]  K. Riabowol,et al.  Monitoring mRNA expression by polymerase chain reaction: the "primer-dropping" method. , 1994, Analytical biochemistry.

[33]  W. Schmalix,et al.  SWH1 from yeast encodes a candidate nuclear factor containing ankyrin repeats and showing homology to mammalian oxysterol-binding protein. , 1994, Biochimica et Biophysica Acta.

[34]  T J Gibson,et al.  PH domain: the first anniversary. , 1994, Trends in biochemical sciences.

[35]  H. Bussey,et al.  A new family of yeast genes implicated in ergosterol synthesis is related to the human oxysterol binding protein , 1994, Yeast.

[36]  P. Dawson,et al.  Translocation of oxysterol binding protein to Golgi apparatus triggered by ligand binding , 1992, The Journal of cell biology.

[37]  U. Francke,et al.  cDNA cloning of human oxysterol-binding protein and localization of the gene to human chromosome 11 and mouse chromosome 19. , 1990, Genomics.

[38]  P. Dawson,et al.  Purification of oxysterol binding protein from hamster liver cytosol. , 1989, The Journal of biological chemistry.

[39]  F. Taylor,et al.  Oxysterol binding protein. , 1985, Chemistry and physics of lipids.

[40]  F. Taylor,et al.  Correlation between oxysterol binding to a cytosolic binding protein and potency in the repression of hydroxymethylglutaryl coenzyme A reductase. , 1984, Journal of Biological Chemistry.

[41]  T. Nagase,et al.  Prediction of the coding sequences of unidentified human genes. XVII. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro. , 2000, DNA research : an international journal for rapid publication of reports on genes and genomes.

[42]  N. Ridgway,et al.  Chinese hamster ovary cells overexpressing the oxysterol binding protein (OSBP) display enhanced synthesis of sphingomyelin in response to 25-hydroxycholesterol. , 1999, Journal of lipid research.

[43]  M. Suyama,et al.  Prediction of the coding sequences of unidentified human genes. X. The complete sequences of 100 new cDNA clones from brain which can code for large proteins in vitro. , 1998, DNA research : an international journal for rapid publication of reports on genes and genomes.

[44]  M. Suyama,et al.  Prediction of the coding sequences of unidentified human genes. XI. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro. , 1998, DNA research : an international journal for rapid publication of reports on genes and genomes.