Disease relevance of SCP2

• Recombinant human sterol carrier protein 2 (SCP2) variants were generated by site-directed mutagenesis and expression in Escherichia coli [1].
• To assess the possibility that sterol carrier protein-2 (SCP-2) is involved in this transport, we studied the time course of newly synthesized cholesterol incorporation in the plasma membrane of normal and SCP-2-deficient (Zellweger syndrome) human fibroblasts [2].
• Mutations in human PAHX cause phytanic acid accumulations leading to Adult Refsum's Disease (ARD), which is also observed in a sterol carrier protein 2 (SCP-2)-deficient mouse model [3].
• In this study, recombinant liver fatty acid binding protein (L-FABP) and sterol carrier protein-2 (SCP-2) were used in conjunction with a series of fluorescent fatty acid probe molecules to compare the relative dielectric properties of the ligand binding sites and to examine the effects of ethanol in vitro on ligand interaction with these proteins [4].
• Overexpression of sterol carrier protein-2 mRNA in patients with cholesterol gallstones [5].

High impact information on SCP2

• Collectively, our results suggest that SCP2 is involved in promoter clearance during steroid-activated transcription [6].
• Ser 5 phosphorylation of the RNA polymerase II CTD, a process necessary for initiation of transcription elongation, occurred significantly earlier in SCP2-silenced than parental LNCaP cells [6].
• In cultured skin fibroblasts, the thiolytic activity of SCPx was deficient, and no SCPx protein could be detected by western blotting [7].
• The predicted effects of the different disease-causing amino acid changes on protein structure were determined using the crystal structures of the (3R)-hydroxyacyl-coenzyme A (CoA) dehydrogenase unit of rat DBP and the 2-enoyl-CoA hydratase 2 unit and liganded sterol carrier protein 2-like unit of human DBP [8].
• Intracellular dissemination of peroxidative stress. Internalization, transport, and lethal targeting of a cholesterol hydroperoxide species by sterol carrier protein-2-overexpressing hepatoma cells [9].

Biological context of SCP2

• Overexpression of ILK in the anoikis-sensitive SCP2 cells results in a profound inhibition of anoikis, as determined by annexin V binding and activation of caspases 8 and 3 [10].
• Holo-sterol carrier protein-2. (13)C NMR investigation of cholesterol and fatty acid binding sites [11].
• We determined the DNA sequence of 3.4 kb of the proximal promoter governing the transcription of SCPx sequences [12].
• The transcriptional regulation of SCPx and SCP2 is unclear, but their promoter regions contain several putative regulatory domains [13].
• The amino acid sequence of the protein suggests that SCPx may function as a thiolase [14].

Anatomical context of SCP2

• In addition to SCPx activity measurements in fibroblasts from patients with a defect in peroxisomal beta-oxidation of unresolved etiology, we studied the stability and activity of SCPx in fibroblasts from patients with Zellweger syndrome, which lack functional peroxisomes [15].
• The specificity of the assay was demonstrated by the finding of a full deficiency in fibroblasts from an SCPx knock-out mouse [15].
• Previous studies showed that the N-terminal 32 amino acids of sterol carrier protein-2 ((1-32)SCP(2)) comprise an amphipathic alpha-helix essential for SCP(2) binding to membranes [Huang et al. (1999) Biochemistry 38, 13231] [16].
• We found that SCPx is not only stable in the cytosol, but displays a higher activity in fibroblasts from patients with Zellweger syndrome than in control fibroblasts [15].
• In contrast, sterol carrier protein-2 (SCP-2) was only 2.2-fold more effective in mediating sterol transfer from steroidogenic cell mitochondria [17].

Associations of SCP2 with chemical compounds

• One hypothesis has been that sterol carrier protein-2 (SCP2, also known as the non-specific lipid transfer protein) acts in cholesterol transport through the cytoplasm [18].
• Recent studies employing gene targeting in mice showed, however, that mice lacking SCP2 and the related putative sterol carrier known as SCPx, develop a defect in peroxisomal beta-oxidation [18].
• In addition, diminished peroxisomal alpha-oxidation of phytanic acid (3,7,11, 15-tetramethylhexadecanoic acid) in these null mice was attributed to the absence of SCP2 which has a number of properties supporting a function as carrier for fatty acyl-CoAs rather than for sterols [18].
• In addition, 8-Br-cAMP and phorbol myristate acetate were found to increase SCPx promoter activity in a host cell-specific manner [12].
• Sterol carrier protein-2, a new fatty acyl coenzyme A-binding protein [19].

Other interactions of SCP2

• The side chain of the bile acid intermediates is shortened via one cycle of beta-oxidation catalyzed by trihydroxycoprostanoyl-CoA oxidase, MFP-2 and SCPX [20].
• 2-Methyl-branched acyl-CoAs are degraded via pristanoyl-CoA oxidase, multifunctional protein-2 (MFP-2) (which displays 2-enoyl-CoA hydratase and D-3-hydroxyacyl-CoA dehydrogenase activities) and sterol carrier protein-X (SCPX; displaying 2-methyl-3-oxoacyl-CoA thiolase activity) [20].
• Utilization of sterol carrier protein-2 by phytanoyl-CoA 2-hydroxylase in the peroxisomal alpha oxidation of phytanic acid [3].
• The second group consists of recently identified enzymes, branched-chain oxidase, the D-bifunctional protein, and sterol-carrier protein x, which catalyze four reactions of beta-oxidation cycle [21].
• We show that SCPX and HSDL2 are present in most animals from Cnidaria to Chordata [22].

Analytical, diagnostic and therapeutic context of SCP2

• Northern blot analysis revealed only a single mRNA species of 1.4 kb, which agrees well with the length of the cDNA (1371 bp), making it improbable that alternative splicing produces an SCPx-like fusion protein [23].
• In contrast, the level of sterol carrier protein 2 (SCP2), a Leydig cell-specific protein, was affected by hypophysectomy much less than the other parameters measured [24].
• However, clofibric acid did not induce peroxisome proliferation in the JEG-3 cells, as assessed by electron microscopy and immunostaining for catalase, a peroxisomal enzyme, or alter levels of mRNAs for peroxisomal proteins, sterol carrier protein-X/sterol carrier protein-2 and acyl-Coenzyme-A oxidase [25].
• Using immunohistochemistry, we detected that CRF-ir cell bodies exist in different brain regions: medulla oblongata (MO), midbrain tegmentum, habenula, nucleus preopticus (NPO), and in a ventral hypothalamic region corresponding to the nucleus lateralis tuberis (NLTP) [26].
• The nonspecific lipid transfer protein (i.e., sterol carrier protein 2) from human liver was purified to homogeneity using ammonium sulfate precipitation, CM-cellulose chromatography, molecular sieve chromatography and fast protein liquid chromatography [27].

References