Philipp Rovina

Philipp Rovina

Wien, Wien, Österreich
2405 Follower:innen 500+ Kontakte

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An executive Leader with strong commercial and operations experience. An expert focus on…

Berufserfahrung

  • Gebr. Brasseler GmbH & Co. KG Grafik

    Gebr. Brasseler GmbH & Co. KG

    Lemgo, Nordrhein-Westfalen, Deutschland

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    Wien, Österreich

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    Wien, Österreich

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    Wien

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    Vienna, Austria

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    Vienna, Austria

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    Vienna, Austria

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    Vienna, Austria

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    Vienna, Austria

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    Vienna, Austria

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Bescheinigungen und Zertifikate

Veröffentlichungen

  • Transcriptional repression of ceramide kinase in LPS-challenged macrophages.

    Biochem Biophys Res Commun. 2010 Oct 8;401(1):164-7.

    Ceramide kinase (CERK) produces the bioactive lipid ceramide 1-phosphate (C1P). Both CERK and C1P have been identified as mediators of cell growth and survival. Recent evidence showed that CERK is down-regulated during M1-type macrophage activation, which is known to promote cell growth arrest. However, the mechanism has not been investigated yet and, in particular, whether growth arrest might be the signal for down-regulation of CERK is currently unknown. Here, we found that LPS-mediated TLR-4…

    Ceramide kinase (CERK) produces the bioactive lipid ceramide 1-phosphate (C1P). Both CERK and C1P have been identified as mediators of cell growth and survival. Recent evidence showed that CERK is down-regulated during M1-type macrophage activation, which is known to promote cell growth arrest. However, the mechanism has not been investigated yet and, in particular, whether growth arrest might be the signal for down-regulation of CERK is currently unknown. Here, we found that LPS-mediated TLR-4 engagement reduces Cerk mRNA levels in mouse primary macrophages. Reporter gene assays in RAW264.7 macrophages showed that LPS inhibits the transcriptional activity of the Cerk proximal promoter. The G1-cell cycle blocker mimosine did not inhibit Cerk transcription, suggesting that transcriptional repression of Cerk by LPS is not a primary consequence of LPS-induced cell cycle blockade.

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  • Modulation of ceramide metabolism in mouse primary macrophages.

    Biochem Biophys Res Commun. 2010 Aug 20;399(2):150-4.

    Ceramide kinase (CERK) produces the bioactive lipid ceramide 1-phosphate (C1P) and is, together with glucosylceramide synthase (GCS) and sphingomyelin synthases (SMS-1 and -2), a key regulator of ceramide metabolism. Here, we used a previously validated assay for measuring CERK, GCS, and SMS activities simultaneously, to study the regulation of ceramide metabolism in mouse macrophages. Elicitation of peritoneal macrophages as well as differentiation of bone marrow-derived monocytes into…

    Ceramide kinase (CERK) produces the bioactive lipid ceramide 1-phosphate (C1P) and is, together with glucosylceramide synthase (GCS) and sphingomyelin synthases (SMS-1 and -2), a key regulator of ceramide metabolism. Here, we used a previously validated assay for measuring CERK, GCS, and SMS activities simultaneously, to study the regulation of ceramide metabolism in mouse macrophages. Elicitation of peritoneal macrophages as well as differentiation of bone marrow-derived monocytes into macrophages led to "ceramide anabolic switching" by re-directing ceramide anabolism towards C1P synthesis by CERK. In contrast, macrophage activation by lipopolysaccharide (LPS) evoked a "ceramide anabolic switch" going in the opposite direction, i.e. featuring up-regulation of GCS and SMS and down-regulation of CERK. The LPS effects were partially blocked by dexamethasone, a known macrophage de-activator. Altogether, the data reveal a contrasting regulation of ceramide metabolism enzymes during macrophage biological responses.

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  • Subcellular localization of ceramide kinase and ceramide kinase-like protein requires interplay of their Pleckstrin Homology domain-containing N-terminal regions together with C-terminal domains.

    Biochim Biophys Acta. 2009 Oct;1791(10):1023-30.

    Ceramide kinase (CERK) and the ceramide kinase-like protein (CERKL), two related members of the diacylglycerol kinase family, are ill-defined at the molecular level. In particular, what determines their distinctive subcellular localization is not well understood. Here we show that the Pleckstrin Homology (PH) domain of CERK, which is required for Golgi complex localization, can substitute for the N-terminal region of CERKL and allow for wild-type CERKL localization, which is typified by…

    Ceramide kinase (CERK) and the ceramide kinase-like protein (CERKL), two related members of the diacylglycerol kinase family, are ill-defined at the molecular level. In particular, what determines their distinctive subcellular localization is not well understood. Here we show that the Pleckstrin Homology (PH) domain of CERK, which is required for Golgi complex localization, can substitute for the N-terminal region of CERKL and allow for wild-type CERKL localization, which is typified by nucleolar accumulation. This demonstrates that determinants for localization of these two enzymes do not lie solely in their PH domain-containing N-terminal regions. Moreover, we present evidence for a previously unrecognized participation of CERK distal sequences in structural stability, localization and activity of the full-length protein. Progressive deletion of CERK and CERKL from the C-terminus revealed similar sequential organization in both proteins, with nuclear import signals in their N-terminal part, and nuclear export signals in their C-terminal part. Furthermore, mutagenesis of individual cysteine residues of a CERK-specific CXXXCXXC motif severely compromised both exportation of CERK from the nucleus and its association with the Golgi complex. Altogether, this work identifies conserved domains in CERK and CERKL as well as new determinants for their subcellular localization. It further suggests a nucleocytoplasmic shuttling mechanism for both proteins that may be defective in CERKL mutant proteins responsible for retinal degenerative diseases.

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  • A critical beta6-beta7 loop in the pleckstrin homology domain of ceramide kinase.

    Biochem J. 2006 Dec 1;400(2):255-65.

    CerK (ceramide kinase) produces ceramide 1-phosphate, a sphingophospholipid with recognized signalling properties. It localizes to the Golgi complex and fractionates essentially between detergent-soluble and -insoluble fractions; however, the determinants are unknown. Here, we made a detailed mutagenesis study of the N-terminal PH domain (pleckstrin homology domain) of CerK, based on modelling, and identified key positively charged amino acid residues within an unusual motif in the loop…

    CerK (ceramide kinase) produces ceramide 1-phosphate, a sphingophospholipid with recognized signalling properties. It localizes to the Golgi complex and fractionates essentially between detergent-soluble and -insoluble fractions; however, the determinants are unknown. Here, we made a detailed mutagenesis study of the N-terminal PH domain (pleckstrin homology domain) of CerK, based on modelling, and identified key positively charged amino acid residues within an unusual motif in the loop interconnecting beta-strands 6 and 7. These residues are critical for CerK membrane association and polyphosphoinositide binding and activity. Their mutagenesis results in increased thermolability, sensitivity to proteolysis, reduced apparent molecular mass as well as propensity of the recombinant mutant protein to aggregate, indicating that this loop impacts the overall conformation of the CerK protein. This is in contrast with most PH domains whose function strongly relies on charges located in the beta1-beta2 loop.

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Patente

  • Ceramide kinase loop

    Ausgestellt am EU WO 2007/088171 A1

    Abstract: An isolated polynucleotide of SEQ ID NO:1, an isolated polypeptide of SEQ ID NO:2, e.g. encoded by a polynucleotide of SEQ ID NO: 1, a vector comprising such polynucleotide, an expression system, comprising such polynucleotide, a host cell comprising such expression system, the use of a such polypeptide or polynucleotide as a diagnostic reagent, screening assays and methods for identifying an agonist or an antagonist of a ceramide kinase by use of such polypeptide or polynucleotide…

    Abstract: An isolated polynucleotide of SEQ ID NO:1, an isolated polypeptide of SEQ ID NO:2, e.g. encoded by a polynucleotide of SEQ ID NO: 1, a vector comprising such polynucleotide, an expression system, comprising such polynucleotide, a host cell comprising such expression system, the use of a such polypeptide or polynucleotide as a diagnostic reagent, screening assays and methods for identifying an agonist or an antagonist of a ceramide kinase by use of such polypeptide or polynucleotide and an agonist or an antagonist of a ceramide kinase obtained by such screening and their use.

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