Cholesterol transport mediated by sterol carrier protein 2 (SCP2)

Seedorf, Udo; Brysch, P.; Engel, Thomas; Scheek, Sigrid; Raabe, Martin; Szyperski, Thomas; ̈thrich, K. Wu; Maeda, Nobuyo; Assmann, Gerd

doi:10.1016/0021-9150(94)93701-x

Cited by 12 publications

(29 citation statements)

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“…In PEX5-deficient mutant cells, SCPx is associated with endomembranes such as peroxisomal remnants and mitochondria. It is noteworthy that not only the 59-kDa form but also the 46-kDa fragment are enzymatically active as a branched-chain fatty acid thiolase (15,17,40), as revealed using specimens from patients with peroxisome-defective disorders such as Zellweger syndrome. Localization of SCPx on endomembranes may be required for such enzymatic activity of the unprocessed form.…”

Section: Resultsmentioning

confidence: 99%

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Biogenesis of Nonspecific Lipid Transfer Protein and Sterol Carrier Protein x

Otera

Nishimura

Setoguchi

et al. 2001

Journal of Biological Chemistry

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Nonspecific lipid transfer protein (nsLTP; also called sterol carrier protein 2) with a molecular mass of 13 kDa is synthesized as a larger 15-kDa precursor (pre-nsLTP) with an N-terminal 20-amino acid extension presequence, as well as with the peroxisome targeting signal type 1 (PTS1), Ala-Lys-Leu, at the C terminus. The precursor pre-nsLTP is processed to mature nsLTP by proteolytic removal of the presequence, most likely after being imported into peroxisomes. Sterol carrier protein x (SCPx), a 59-kDa branched-chain fatty acid thiolase of peroxisomes, contains the entire pre-nsLTP moiety at the C-terminal part and is converted to the 46-kDa form and nsLTP after the transport to peroxisomes. We investigated which of these two potential topogenic sequences functions in biogenesis of nsLTP and SCPx. Morphological and biochemical analyses, making use of Chinese hamster ovary cell pex mutants such as the PTS1 receptor-impaired pex5 and PTS2 import-defective pex7, as well as green fluorescent protein chimeras, revealed that both pre-nsLTP and SCPx are imported into peroxisomes by the Pex5p-mediated PTS1 pathway. Nearly half of the pre-nsLTP remains in the cytosol, as assessed by subcellular fractionation of the wild-type Chinese hamster ovary cells. In an in vitro binding assay, only mature nsLTP, but not pre-nsLTP, from the cell lysates interacted with the Pex5p. It is likely, therefore, that modulation of the C-terminal PTS1 by the presequence gives rise to cytoplasmic localization of prensLTP.

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Section: Resultsmentioning

confidence: 99%

“…The sequence for SCPx contains the full sequence of pre-nsLTP at the C-terminal part and is suggested to be partly converted to the N-terminal part protein of 46 kDa and nsLTP (1,14). It has been demonstrated that SCPx functions as a peroxisomal branched-chain ␤-ketothiolase (15)(16)(17).…”

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confidence: 99%

Biogenesis of Nonspecific Lipid Transfer Protein and Sterol Carrier Protein x

Otera

Nishimura

Setoguchi

et al. 2001

Journal of Biological Chemistry

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“…Indeed, residues of SCPx and both mitochondrial and peroxi-SCP2 has been found to promote the exchange of vari-somal 3-oxoacyl-CoA thiolase [11,18,23]. Direct activous lipids and sterols between membranes, stimulates ity measurements showed that SCPx, indeed, posthe enzymatic conversion of 7-dehydrocholesterol to sesses 3-oxoacyl-CoA thiolase activity next to its intrinsic sterol carrier protein and lipid transfer activity [24]. The substrate specificity of SCPx, how-conventional peroxisomal thiolase characterized by solution followed by acetonitrile (final concentration: 40% (v/v).…”

Section: Academic Pressmentioning

confidence: 99%

“…[25] MATERIALS AND METHODS and SCPx [24]. The peroxisome proliferator-inducible thiolase was purified to apparent homogeneity on SDS/PAGE from clofibrate-…”

Section: Academic Pressmentioning

confidence: 99%

Sterol Carrier Protein X (SCPx) Is a Peroxisomal Branched-Chain β-Ketothiolase Specifically Reacting with 3-Oxo-pristanoyl-CoA: A New, Unique Role for SCPx in Branched-Chain Fatty Acid Metabolism in Peroxisomes

Wanders

Denis

Wouters

et al. 1997

Biochemical and Biophysical Research Communications

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cholesterol in microsomes and also the acyltransferase One of the most important functions of peroxisomes, mediated esterification of intracellular cholesterol [1]. at least in humans, is the b-oxidation of a range of Moreover, in steroid hormone producing cells SCP2 is different fatty acids and fatty acid derivatives. Recent thought to facilitate the transport of cholesterol to mistudies have shown that the enzymatic machinery re-tochondria, where the first committed step in the forquired for the b-oxidations of these substrates, may mation of pregnenolone takes place [2][3][4][5].be much more complex as originally thought. We now SCP2 has been purified from a variety of sources report that the conventional peroxisomal thiolase and its structure appears to be highly conserved Firstly, the antibody raised not only for the functional organization of the peroxi-against SCP2 was found to crossreact with a higher somal b-oxidation system but also for studies dealing molecular mass protein of 58 kDa [6,7,[14][15][16]. In adwith the resolution of the underlying defect in patients dition, the livers of all mammalian species studied with some defect in peroxisomal b-oxidation. ᭧ 1997 contain SCP2-related transcripts encoding for larger Academic Pressproteins that were found to be identical to pre-SCP2 at their C-terminal domains [8-13; 18-21]. It is now clear that the 58 kDa protein called SCPx [1] and the 14.5 kDa pre-SCP2 are the products of different Sterol carrier protein 2 (SCP2), alternatively called mRNAs produced from the same gene which has two non-specific lipid transfer protein (nsLTP) is a small promoters [22]. Interestingly, significant sequence basic protein assumed to participate in the intracellu-homology was found between the first 400 amino acid lar transport of sterols and other lipids [1]. Indeed, residues of SCPx and both mitochondrial and peroxi-SCP2 has been found to promote the exchange of vari-somal 3-oxoacyl-CoA thiolase [11,18,23]. Direct activous lipids and sterols between membranes, stimulates ity measurements showed that SCPx, indeed, posthe enzymatic conversion of 7-dehydrocholesterol to sesses 3-oxoacyl-CoA thiolase activity next to its intrinsic sterol carrier protein and lipid transfer activity [24]. The substrate specificity of SCPx, how-

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“…The SCP2 gene (Scp2) codes not only for SCP2, but also for a fused protein of 60 kDa called sterol carrier protein-x (SCPx) (5,6). The C-terminal domain of SCPx is identical with SCP2 whereas its Nterminal part consists of an active ␤-ketothiolase (7,8). The two proteins are expressed from a common gene via alternative transcription initiation at two separated promoters (9).…”

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confidence: 99%