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  1. Article ; Online: Localisation of keratin K78 in the basal layer and first suprabasal layers of stratified epithelia completes expression catalogue of type II keratins and provides new insights into sequential keratin expression.

    Langbein, Lutz / Eckhart, Leopold / Fischer, Heinz / Rogers, Michael A / Praetzel-Wunder, Silke / Parry, David A D / Kittstein, Walter / Schweizer, Juergen

    Cell and tissue research

    2016  Volume 363, Issue 3, Page(s) 735–750

    Abstract: Among the 26 human type II keratins, K78 is the only one that has not yet been explored with regard to its expression characteristics. Here, we show that, at both the transcriptional and translational levels, K78 is strongly expressed in the basal and ... ...

    Abstract Among the 26 human type II keratins, K78 is the only one that has not yet been explored with regard to its expression characteristics. Here, we show that, at both the transcriptional and translational levels, K78 is strongly expressed in the basal and parabasal cell layers with decreasing intensity in the lower suprabasal cells of keratinising and non-keratinising squamous epithelia and keratinocyte cultures. The same pattern has been detected at the transcriptional level in the corresponding mouse epithelia. Murine K78 protein, which contains an extraordinary large extension of its tail domain, which is unique among all known keratins, is not detectable by the antibody used. Concomitant studies in human epithelia have confirmed K78 co-expression with the classical basal keratins K5 and K14. Similarly, K78 co-expression with the differentiation-related type I keratins K10 (epidermis) and K13 (non-keratinising epithelia) occurs in the parabasal cell layer, whereas that of the corresponding type II keratins K1 (epidermis) and K4 (non-keratinising epithelia) unequivocally starts subsequent to the respective type I keratins. Our data concerning K78 expression modify the classical concept of keratin pair K5/K14 representing the basal compartment and keratin pairs K1/K10 or K4/K13 defining the differentiating compartment of stratified epithelia. Moreover, the K78 expression pattern and the decoupled K1/K10 and K4/K13 expression define the existence of a hitherto unperceived early differentiation stage in the parabasal layer characterized by K78/K10 or K78/K13 expression.
    MeSH term(s) Adult ; Amino Acid Sequence ; Animals ; Carcinoma, Squamous Cell/metabolism ; Carcinoma, Squamous Cell/pathology ; Embryonic Development ; Epidermis/metabolism ; Epithelium/metabolism ; Evolution, Molecular ; Fluorescent Antibody Technique ; Gene Expression Regulation ; Genetic Loci ; Humans ; In Situ Hybridization ; Keratinocytes/metabolism ; Keratins, Type II/chemistry ; Keratins, Type II/genetics ; Keratins, Type II/metabolism ; Mice, Inbred C57BL ; Molecular Sequence Data ; Protein Transport ; RNA, Messenger/genetics ; RNA, Messenger/metabolism ; Sequence Analysis, Protein
    Chemical Substances Keratins, Type II ; RNA, Messenger
    Language English
    Publishing date 2016-03
    Publishing country Germany
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 125067-x
    ISSN 1432-0878 ; 0302-766X
    ISSN (online) 1432-0878
    ISSN 0302-766X
    DOI 10.1007/s00441-015-2278-5
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: New facets of keratin K77: interspecies variations of expression and different intracellular location in embryonic and adult skin of humans and mice.

    Langbein, Lutz / Reichelt, Julia / Eckhart, Leopold / Praetzel-Wunder, Silke / Kittstein, Walter / Gassler, Nikolaus / Schweizer, Juergen

    Cell and tissue research

    2013  Volume 354, Issue 3, Page(s) 793–812

    Abstract: The differential expression of keratins is central to the formation of various epithelia and their appendages. Structurally, the type II keratin K77 is closely related to K1, the prototypical type II keratin of the suprabasal epidermis. Here, we perform ... ...

    Abstract The differential expression of keratins is central to the formation of various epithelia and their appendages. Structurally, the type II keratin K77 is closely related to K1, the prototypical type II keratin of the suprabasal epidermis. Here, we perform a developmental study on K77 expression in human and murine skin. In both species, K77 is expressed in the suprabasal fetal epidermis. While K77 appears after K1 in the human epidermis, the opposite is true for the murine tissue. This species-specific pattern of expression is also found in conventional and organotypic cultures of human and murine keratinocytes. Ultrastructure investigation shows that, in contrast to K77 intermediate filaments of mice, those of the human ortholog are not attached to desmosomes. After birth, K77 disappears without deleterious consequences from human epidermis while it is maintained in the adult mouse epidermis, where its presence has so far gone unnoticed. After targeted Krt1 gene deletion in mice, K77 is normally expressed but fails to functionally replace K1. Besides the epidermis, both human and mouse K77 are present in luminal duct cells of eccrine sweat glands. The demonstration of a K77 ortholog in platypus but not in non-mammalian vertebrates identifies K77 as an evolutionarily ancient component of the mammalian integument that has evolved different patterns of intracellular distribution and adult tissue expression in primates.
    MeSH term(s) Amino Acid Sequence ; Animals ; Cell Adhesion/physiology ; Epidermis/chemistry ; Epidermis/cytology ; Epidermis/embryology ; Epidermis/metabolism ; Gorilla gorilla ; Humans ; Keratinocytes/chemistry ; Keratinocytes/cytology ; Keratinocytes/metabolism ; Keratins/biosynthesis ; Keratins/chemistry ; Keratins/genetics ; Keratins/metabolism ; Mice ; Mice, Knockout ; Microscopy, Immunoelectron ; Molecular Sequence Data ; RNA, Messenger/biosynthesis ; Skin/chemistry ; Skin/cytology ; Skin/embryology ; Skin/metabolism ; Subcellular Fractions/chemistry ; Subcellular Fractions/metabolism
    Chemical Substances RNA, Messenger ; Keratins (68238-35-7)
    Language English
    Publishing date 2013-12
    Publishing country Germany
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 125067-x
    ISSN 1432-0878 ; 0302-766X
    ISSN (online) 1432-0878
    ISSN 0302-766X
    DOI 10.1007/s00441-013-1716-5
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Against the rules: human keratin K80: two functional alternative splice variants, K80 and K80.1, with special cellular localization in a wide range of epithelia.

    Langbein, Lutz / Eckhart, Leopold / Rogers, Michael A / Praetzel-Wunder, Silke / Schweizer, Juergen

    The Journal of biological chemistry

    2010  Volume 285, Issue 47, Page(s) 36909–36921

    Abstract: Of the 54 human keratins, five members have, at present, only been characterized at the gene level. In this study we have investigated the expression patterns of keratin K80, whose gene is located at the centromeric end of the type II keratin gene domain. ...

    Abstract Of the 54 human keratins, five members have, at present, only been characterized at the gene level. In this study we have investigated the expression patterns of keratin K80, whose gene is located at the centromeric end of the type II keratin gene domain. K80 possesses a number of highly unusual properties. Structurally, it is distinctly closer to type II hair keratins than to type II epithelial keratins. Nonetheless, it is found in virtually all types of epithelia (stratified keratinizing/non-keratinizing, hard-keratinizing, as well as non-stratified tissues, and cell cultures thereof). This conspicuously broad expression range implies an unprecedented in vivo promiscuity of K80, which involves more than 20 different type I partners for intermediate filament (IF) formation. Throughout, K80 expression is related to advanced tissue or cell differentiation. However, instead of being part of the cytoplasmic IF network, K80 containing IFs are located at the cell margins close to the desmosomal plaques, where they are tightly interlaced with the cytoplasmic IF bundles abutting there. In contrast, in cells entering terminal differentiation, K80 adopts the "conventional" cytoplasmic distribution. In evolutionary terms, K80 is one of the oldest keratins, demonstrable down to fish. In addition, KRT80 mRNA is subject to alternative splicing. Besides K80, we describe a smaller but fully functional splice variant K80.1, which arose only during mammalian evolution. Remarkably, unlike the widely expressed K80, the expression of K80.1 is restricted to soft and hard keratinizing epithelial structures of the hair follicle and the filiform tongue papilla.
    MeSH term(s) Alternative Splicing ; Animals ; Blotting, Western ; Cattle ; Cell Differentiation ; Cells, Cultured ; Epithelium/metabolism ; Guinea Pigs ; Hair/cytology ; Hair/metabolism ; Humans ; In Situ Hybridization ; Keratinocytes/cytology ; Keratinocytes/metabolism ; Keratins, Type II/genetics ; Keratins, Type II/immunology ; Keratins, Type II/metabolism ; Mice ; Microscopy, Immunoelectron ; Peptide Fragments/immunology ; RNA, Messenger/genetics ; Skin/cytology ; Skin/metabolism
    Chemical Substances Keratins, Type II ; Peptide Fragments ; RNA, Messenger
    Language English
    Publishing date 2010-09-15
    Publishing country United States
    Document type Comparative Study ; Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2997-x
    ISSN 1083-351X ; 0021-9258
    ISSN (online) 1083-351X
    ISSN 0021-9258
    DOI 10.1074/jbc.M110.161745
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article: Microbial type I fatty acid synthases (FAS): major players in a network of cellular FAS systems.

    Schweizer, Eckhart / Hofmann, Jörg

    Microbiology and molecular biology reviews : MMBR

    2004  Volume 68, Issue 3, Page(s) 501–17, table of contents

    Abstract: The present review focuses on microbial type I fatty acid synthases (FASs), demonstrating their structural and functional diversity. Depending on their origin and biochemical function, multifunctional type I FAS proteins form dimers or hexamers with ... ...

    Abstract The present review focuses on microbial type I fatty acid synthases (FASs), demonstrating their structural and functional diversity. Depending on their origin and biochemical function, multifunctional type I FAS proteins form dimers or hexamers with characteristic organization of their catalytic domains. A single polypeptide may contain one or more sets of the eight FAS component functions. Alternatively, these functions may split up into two different and mutually complementing subunits. Targeted inactivation of the individual yeast FAS acylation sites allowed us to define their roles during the overall catalytic process. In particular, their pronounced negative cooperativity is presumed to coordinate the FAS initiation and chain elongation reactions. Expression of the unlinked genes, FAS1 and FAS2, is in part constitutive and in part subject to repression by the phospholipid precursors inositol and choline. The interplay of the involved regulatory proteins, Rap1, Reb1, Abf1, Ino2/Ino4, Opi1, Sin3 and TFIIB, has been elucidated in considerable detail. Balanced levels of subunits alpha and beta are ensured by an autoregulatory effect of FAS1 on FAS2 expression and by posttranslational degradation of excess FAS subunits. The functional specificity of type I FAS multienzymes usually requires the presence of multiple FAS systems within the same cell. De novo synthesis of long-chain fatty acids, mitochondrial fatty acid synthesis, acylation of certain secondary metabolites and coenzymes, fatty acid elongation, and the vast diversity of mycobacterial lipids each result from specific FAS activities. The microcompartmentalization of FAS activities in type I multienzymes may thus allow for both the controlled and concerted action of multiple FAS systems within the same cell.
    MeSH term(s) Corynebacterium/enzymology ; Fatty Acid Synthases/metabolism ; Fatty Acids/biosynthesis ; Fungi/enzymology ; Gene Expression Regulation, Bacterial ; Gene Expression Regulation, Fungal ; Mycobacterium tuberculosis/enzymology ; Mycolic Acids/metabolism
    Chemical Substances Fatty Acids ; Mycolic Acids ; Fatty Acid Synthases (EC 2.3.1.85)
    Language English
    Publishing date 2004-09-07
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 1376131-6
    ISSN 1098-5557 ; 1070-6275 ; 1092-2172
    ISSN (online) 1098-5557 ; 1070-6275
    ISSN 1092-2172
    DOI 10.1128/MMBR.68.3.501-517.2004
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Book: Industrieraps Biotechnologie

    Schweizer, Eckhart

    Teilvorhaben 8: Umprogrammierung der Fettsäuresynthese in Hefe in Richtung Kürzerkettiger Produkte : [Abschlußbericht zum Forschungsvorhaben 0319170B] ; Abschlußdatum des Vorhabens: 31.1.1993

    1993  

    Author's details Autor: Eckhart Schweizer
    Language German
    Size [12] Bl, graph. Darst
    Publisher Univ., Lehrstuhl f. Biochemie
    Publishing place Erlangen
    Document type Book
    Database Library catalogue of the German National Library of Science and Technology (TIB), Hannover

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  6. Article: New facets of keratin K77: interspecies variations of expression and different intracellular location in embryonic and adult skin of humans and mice

    Langbein, Lutz / Reichelt, Julia / Eckhart, Leopold / Praetzel-Wunder, Silke / Kittstein, Walter / Gassler, Nikolaus / Schweizer, Juergen

    Cell and tissue research. 2013 Dec., v. 354, no. 3

    2013  

    Abstract: The differential expression of keratins is central to the formation of various epithelia and their appendages. Structurally, the type II keratin K77 is closely related to K1, the prototypical type II keratin of the suprabasal epidermis. Here, we perform ... ...

    Abstract The differential expression of keratins is central to the formation of various epithelia and their appendages. Structurally, the type II keratin K77 is closely related to K1, the prototypical type II keratin of the suprabasal epidermis. Here, we perform a developmental study on K77 expression in human and murine skin. In both species, K77 is expressed in the suprabasal fetal epidermis. While K77 appears after K1 in the human epidermis, the opposite is true for the murine tissue. This species-specific pattern of expression is also found in conventional and organotypic cultures of human and murine keratinocytes. Ultrastructure investigation shows that, in contrast to K77 intermediate filaments of mice, those of the human ortholog are not attached to desmosomes. After birth, K77 disappears without deleterious consequences from human epidermis while it is maintained in the adult mouse epidermis, where its presence has so far gone unnoticed. After targeted Krt1 gene deletion in mice, K77 is normally expressed but fails to functionally replace K1. Besides the epidermis, both human and mouse K77 are present in luminal duct cells of eccrine sweat glands. The demonstration of a K77 ortholog in platypus but not in non-mammalian vertebrates identifies K77 as an evolutionarily ancient component of the mammalian integument that has evolved different patterns of intracellular distribution and adult tissue expression in primates.
    Keywords Primates ; adults ; appendages ; desmosomes ; gene deletion ; gene expression regulation ; humans ; integument ; intermediate filaments ; keratin ; keratinocytes ; mice ; sweat glands ; ultrastructure
    Language English
    Dates of publication 2013-12
    Size p. 793-812.
    Publishing place Springer-Verlag
    Document type Article
    ZDB-ID 125067-x
    ISSN 1432-0878 ; 0302-766X
    ISSN (online) 1432-0878
    ISSN 0302-766X
    DOI 10.1007/s00441-013-1716-5
    Database NAL-Catalogue (AGRICOLA)

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  7. Article: Against the Rules: Human Keratin K80: TWO FUNCTIONAL ALTERNATIVE SPLICE VARIANTS, K80 AND K80.1, WITH SPECIAL CELLULAR LOCALIZATION IN A WIDE RANGE OF EPITHELIA

    Langbein, Lutz / Eckhart, Leopold / Rogers, Michael A / Praetzel-Wunder, Silke / Schweizer, Juergen

    Journal of biological chemistry. 2010 Nov. 19, v. 285, no. 47

    2010  

    Abstract: Of the 54 human keratins, five members have, at present, only been characterized at the gene level. In this study we have investigated the expression patterns of keratin K80, whose gene is located at the centromeric end of the type II keratin gene domain. ...

    Abstract Of the 54 human keratins, five members have, at present, only been characterized at the gene level. In this study we have investigated the expression patterns of keratin K80, whose gene is located at the centromeric end of the type II keratin gene domain. K80 possesses a number of highly unusual properties. Structurally, it is distinctly closer to type II hair keratins than to type II epithelial keratins. Nonetheless, it is found in virtually all types of epithelia (stratified keratinizing/non-keratinizing, hard-keratinizing, as well as non-stratified tissues, and cell cultures thereof). This conspicuously broad expression range implies an unprecedented in vivo promiscuity of K80, which involves more than 20 different type I partners for intermediate filament (IF) formation. Throughout, K80 expression is related to advanced tissue or cell differentiation. However, instead of being part of the cytoplasmic IF network, K80 containing IFs are located at the cell margins close to the desmosomal plaques, where they are tightly interlaced with the cytoplasmic IF bundles abutting there. In contrast, in cells entering terminal differentiation, K80 adopts the "conventional" cytoplasmic distribution. In evolutionary terms, K80 is one of the oldest keratins, demonstrable down to fish. In addition, KRT80 mRNA is subject to alternative splicing. Besides K80, we describe a smaller but fully functional splice variant K80.1, which arose only during mammalian evolution. Remarkably, unlike the widely expressed K80, the expression of K80.1 is restricted to soft and hard keratinizing epithelial structures of the hair follicle and the filiform tongue papilla.
    Language English
    Dates of publication 2010-1119
    Size p. 36909-36921.
    Publishing place American Society for Biochemistry and Molecular Biology
    Document type Article
    ZDB-ID 2997-x
    ISSN 1083-351X ; 0021-9258
    ISSN (online) 1083-351X
    ISSN 0021-9258
    Database NAL-Catalogue (AGRICOLA)

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  8. Article: ISC1-encoded inositol phosphosphingolipid phospholipase C is involved in Na+/Li+ halotolerance of Saccharomyces cerevisiae.

    Betz, Christian / Zajonc, Dirk / Moll, Matthias / Schweizer, Eckhart

    European journal of biochemistry

    2002  Volume 269, Issue 16, Page(s) 4033–4039

    Abstract: In Saccharomyces cerevisiae, toxic concentrations of Na+ orLi+ ions induce the expression of the cation-extrusion ATPase gene, ENA1. Several well-studied signal transduction pathways are known correlating high salinity to the transcriptional activation ... ...

    Abstract In Saccharomyces cerevisiae, toxic concentrations of Na+ orLi+ ions induce the expression of the cation-extrusion ATPase gene, ENA1. Several well-studied signal transduction pathways are known correlating high salinity to the transcriptional activation of ENA1. Nevertheless, information on the actual sensing mechanism initiating these pathways is limited. Here, we report that the ISC1-encoded phosphosphingolipid-specific phospholipase C appears to be involved in stimulation of ENA1 expression and, consequently, in mediating Na+ and Li+ tolerance in yeast. Deletion of ISC1 distinctly decreased cellular Na+ and Li+ tolerance as growth of the Deltaisc1::HIS5 mutant, DZY1, was severely impaired by 0.5 m NaCl or 0.01 m LiCl. In contrast,K+ tolerance and general osmostress regulation wereunaffected. Isc1Delta mutant growth with 0.9 m KCl and glycerol accumulation in the presence of 0.9 m NaCl or 1.5 m sorbitol were comparable to that of the wild-type. ENA1-lacZ reporter studies suggested that the increased salt sensitivity of the isc1Delta mutant is related to a significant reduction of Na+/Li+-stimulated ENA1 expression. Correspondingly, Ena1p-dependent extrusion of Na+/Li+ ions was less efficient in the isc1Delta mutant than in wild-type cells. Itis suggested that ISC1-dependent hydrolysis of an unidentified yeast inositol phosphosphingolipid represents an early event in one of the salt-induced signalling pathways of ENA1 transcriptional activation.
    MeSH term(s) Adenosine Triphosphatases/biosynthesis ; Adenosine Triphosphatases/genetics ; Cation Transport Proteins ; Drug Resistance, Fungal ; Gene Expression Regulation, Fungal/physiology ; Glycerol/metabolism ; Lithium Chloride/pharmacology ; Osmolar Concentration ; Osmotic Pressure ; Phospholipases/physiology ; Potassium Chloride/pharmacology ; Saccharomyces cerevisiae/drug effects ; Saccharomyces cerevisiae/enzymology ; Saccharomyces cerevisiae Proteins/biosynthesis ; Saccharomyces cerevisiae Proteins/genetics ; Saccharomyces cerevisiae Proteins/physiology ; Saline Solution, Hypertonic/pharmacology ; Sodium Chloride/pharmacology ; Sodium-Potassium-Exchanging ATPase ; Sorbitol/pharmacology ; Sphingolipids/physiology ; Sphingomyelin Phosphodiesterase/metabolism ; Type C Phospholipases
    Chemical Substances Cation Transport Proteins ; ENA1 protein, S cerevisiae ; Saccharomyces cerevisiae Proteins ; Saline Solution, Hypertonic ; Sphingolipids ; Sodium Chloride (451W47IQ8X) ; Sorbitol (506T60A25R) ; Potassium Chloride (660YQ98I10) ; Phospholipases (EC 3.1.-) ; ISC1 protein, S cerevisiae (EC 3.1.4.-) ; Type C Phospholipases (EC 3.1.4.-) ; Sphingomyelin Phosphodiesterase (EC 3.1.4.12) ; Adenosine Triphosphatases (EC 3.6.1.-) ; Sodium-Potassium-Exchanging ATPase (EC 3.6.3.9) ; Lithium Chloride (G4962QA067) ; Glycerol (PDC6A3C0OX)
    Language English
    Publishing date 2002-08-09
    Publishing country England
    Document type Comparative Study ; Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 3032-6
    ISSN 1432-1033 ; 0014-2956
    ISSN (online) 1432-1033
    ISSN 0014-2956
    DOI 10.1046/j.1432-1033.2002.03096.x
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article: ISC1‐encoded inositol phosphosphingolipid phospholipase C is involved in Na+/Li+ halotolerance of Saccharomyces cerevisiae

    Betz, Christian / Zajonc, Dirk / Moll, Matthias / Schweizer, Eckhart

    European journal of biochemistry. 2002 Aug., v. 269, no. 16

    2002  

    Abstract: In Saccharomyces cerevisiae, toxic concentrations of Na+ orLi+ ions induce the expression of the cation‐extrusion ATPase gene, ENA1. Several well‐studied signal transduction pathways are known correlating high salinity to the transcriptional activation ... ...

    Abstract In Saccharomyces cerevisiae, toxic concentrations of Na+ orLi+ ions induce the expression of the cation‐extrusion ATPase gene, ENA1. Several well‐studied signal transduction pathways are known correlating high salinity to the transcriptional activation of ENA1. Nevertheless, information on the actual sensing mechanism initiating these pathways is limited. Here, we report that the ISC1‐encoded phosphosphingolipid‐specific phospholipase C appears to be involved in stimulation of ENA1 expression and, consequently, in mediating Na+ and Li+ tolerance in yeast. Deletion of ISC1 distinctly decreased cellular Na+ and Li+ tolerance as growth of the Δisc1::HIS5 mutant, DZY1, was severely impaired by 0.5 m NaCl or 0.01 m LiCl. In contrast,K+ tolerance and general osmostress regulation wereunaffected. Isc1Δ mutant growth with 0.9 m KCl and glycerol accumulation in the presence of 0.9 m NaCl or 1.5 m sorbitol were comparable to that of the wild‐type. ENA1‐lacZ reporter studies suggested that the increased salt sensitivity of the isc1Δ mutant is related to a significant reduction of Na+/Li+‐stimulated ENA1 expression. Correspondingly, Ena1p‐dependent extrusion of Na+/Li+ ions was less efficient in the isc1Δ mutant than in wild‐type cells. Itis suggested that ISC1‐dependent hydrolysis of an unidentified yeast inositol phosphosphingolipid represents an early event in one of the salt‐induced signalling pathways of ENA1 transcriptional activation.
    Keywords Saccharomyces cerevisiae ; adenosinetriphosphatase ; extrusion ; genes ; glycerol ; hydrolysis ; ions ; lithium chloride ; mutants ; myo-inositol ; phospholipase C ; potassium chloride ; salinity ; salt tolerance ; signal transduction ; sodium ; sodium chloride ; sorbitol ; toxicity ; transcriptional activation ; yeasts
    Language English
    Dates of publication 2002-08
    Size p. 4033-4039.
    Publishing place Blackwell Science Ltd
    Document type Article
    ZDB-ID 3032-6
    ISSN 1432-1033 ; 0014-2956
    ISSN (online) 1432-1033
    ISSN 0014-2956
    DOI 10.1046/j.1432-1033.2002.03096.x
    Database NAL-Catalogue (AGRICOLA)

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  10. Article: Cloning, expression, and characterization of the human mitochondrial beta-ketoacyl synthase. Complementation of the yeast CEM1 knock-out strain.

    Zhang, Lei / Joshi, Anil K / Hofmann, Jörg / Schweizer, Eckhart / Smith, Stuart

    The Journal of biological chemistry

    2005  Volume 280, Issue 13, Page(s) 12422–12429

    Abstract: A human beta-ketoacyl synthase implicated in a mitochondrial pathway for fatty acid synthesis has been identified, cloned, expressed, and characterized. Sequence analysis indicates that the protein is more closely related to freestanding counterparts ... ...

    Abstract A human beta-ketoacyl synthase implicated in a mitochondrial pathway for fatty acid synthesis has been identified, cloned, expressed, and characterized. Sequence analysis indicates that the protein is more closely related to freestanding counterparts found in prokaryotes and chloroplasts than it is to the beta-ketoacyl synthase domain of the human cytosolic fatty acid synthase. The full-length nuclear-encoded 459-residue protein includes an N-terminal sequence element of approximately 38 residues that functions as a mitochondrial targeting sequence. The enzyme can elongate acyl-chains containing 2-14 carbon atoms with malonyl moieties attached in thioester linkage to the human mitochondrial acyl carrier protein and is able to restore growth to the respiratory-deficient yeast mutant cem1 that lacks the endogenous mitochondrial beta-ketoacyl synthase and exhibits lowered lipoic acid levels. To date, four components of a putative type II mitochondrial fatty acid synthase pathway have been identified in humans: acyl carrier protein, malonyl transferase, beta-ketoacyl synthase, and enoyl reductase. The substrate specificity and complementation data for the beta-ketoacyl synthase suggest that, as in plants and fungi, in humans this pathway may play an important role in the generation of octanoyl-acyl carrier protein, the lipoic acid precursor, as well as longer chain fatty acids that are required for optimal mitochondrial function.
    MeSH term(s) 3-Oxoacyl-(Acyl-Carrier-Protein) Synthase/biosynthesis ; 3-Oxoacyl-(Acyl-Carrier-Protein) Synthase/chemistry ; 3-Oxoacyl-(Acyl-Carrier-Protein) Synthase/genetics ; Amino Acid Sequence ; Animals ; Cell Nucleus/metabolism ; Cerulenin/chemistry ; Cloning, Molecular ; DNA Primers/chemistry ; DNA, Complementary/metabolism ; Dose-Response Relationship, Drug ; Esters/chemistry ; Genetic Complementation Test ; Humans ; Kinetics ; Mass Spectrometry ; Mice ; Mitochondria/enzymology ; Mitochondria/metabolism ; Molecular Sequence Data ; Phylogeny ; Protein Structure, Tertiary ; Sequence Homology, Amino Acid ; Substrate Specificity ; Thioctic Acid/chemistry ; Tissue Distribution
    Chemical Substances DNA Primers ; DNA, Complementary ; Esters ; Cerulenin (17397-89-6) ; Thioctic Acid (73Y7P0K73Y) ; 3-Oxoacyl-(Acyl-Carrier-Protein) Synthase (EC 2.3.1.41)
    Language English
    Publishing date 2005-01-24
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, P.H.S.
    ZDB-ID 2997-x
    ISSN 1083-351X ; 0021-9258
    ISSN (online) 1083-351X
    ISSN 0021-9258
    DOI 10.1074/jbc.M413686200
    Database MEDical Literature Analysis and Retrieval System OnLINE

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