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  • 1. Fischer, H
    et al.
    Zhang, X U
    O'Brien, K P
    Kylsten, Per
    Södertörns högskola, Avdelning Naturvetenskap.
    Engvall, E
    C7, a novel nucleolar protein, is the mouse homologue of the Drosophila late puff product L82 and an isoform of human OXR12001Ingår i: Biochemical and Biophysical Research Communications - BBRC, ISSN 0006-291X, E-ISSN 1090-2104, Vol. 281, nr 3, s. 795-803Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The C7 gene was identified in a project aimed to characterize differential gene expression upon attachment of cells to extracellular matrix proteins in vitro. C7 is the homologue of Drosophila L82, a late puff gene (Stowers et al. (1999) Dev. Biol. 213, 116-130) and human OXR1, a gene, which protects cells against oxidation (Volkert et al. (2000) Proc. Natl. Acad. Sci. USA 97, 14530-14535). All are transcribed into multiple splice forms with a common 3' domain. Additional members of this novel gene family are found in a number of eukaryotic species. In the mouse, the C7 gene is highly and broadly expressed during development in at least 4 splice forms, 3 of which were sequenced. In the adult, the C7 gene is most highly expressed in brain and testis. Antibodies to recombinant C7 protein localized to nucleoli in a variety of cell types, suggesting that C7 may be involved in the formation or function of this important organelle.

  • 2.
    Gallio, Marco
    et al.
    Södertörns högskola, Institutionen för kemi, biologi, geografi och miljövetenskap. Stockholm University / Karolinska Institute.
    Englund, C
    Stockholm University / Umeå University.
    Kylsten, Per
    Södertörns högskola, Institutionen för kemi, biologi, geografi och miljövetenskap.
    Samakovlis, C
    Stockholm University.
    Rhomboid 3 orchestrates Slit-independent repulsion of tracheal branches at the CNS midline2004Ingår i: Development, ISSN 0950-1991, E-ISSN 1477-9129, Vol. 131, nr 15, s. 3605-3614Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    EGF-receptor ligands act as chemoattractants for migrating epithelial cells during organogenesis and wound healing. We present evidence that Rhomboid 3/EGF signalling, which originates from the midline of the Drosophila ventral nerve cord, repels tracheal ganglionic branches and prevents them from crossing it. rho3 acts independently from the main midline repellent Slit, and originates from a different sub-population of midline cells: the VUM neurons. Expression of dominant-negative Egfr or Ras induces midline crosses, whereas activation of the Egfr or Ras in the leading cell of the ganglionic branch can induce premature turns away from the midline. This suggests that the level of Egfr intracellular signalling, rather than the asymmetric activation of the receptor on the cell surface, is an important determinant in ganglionic branch repulsion. We propose that Egfr activation provides a necessary switch for the interpretation of a yet unknown repellent function of the midline.

  • 3.
    Gallio, Marco
    et al.
    Södertörns högskola, Avdelning Naturvetenskap. Karolinska Institutet.
    Kylsten, Per
    Södertörns högskola, Avdelning Naturvetenskap. Karolinska Institutet.
    Providencia may help find a function for a novel, widespread protein family2000Ingår i: Current Biology, ISSN 0960-9822, E-ISSN 1879-0445, Vol. 10, nr 19, s. R693-R694Artikel i tidskrift (Refereegranskat)
  • 4.
    Gallio, Marco
    et al.
    Södertörns högskola, Institutionen för kemi, biologi, geografi och miljövetenskap. Karolinska Institutet.
    Kylsten, Per
    Södertörns högskola, Institutionen för kemi, biologi, geografi och miljövetenskap.
    The roughoid locus identifies a novel function involved in epidermal growth factor receptor signalling in DrosophilaManuskript (preprint) (Övrigt vetenskapligt)
  • 5.
    Gallio, Marco
    et al.
    Södertörns högskola, Avdelning Naturvetenskap. Karolinska Institute.
    Sturgill, G
    Case Western Reserve University School of Medicine, Cleveland, USA.
    Rather, P
    Case Western Reserve University School of Medicine, Cleveland, USA.
    Kylsten, Per
    Södertörns högskola, Avdelning Naturvetenskap.
    A conserved mechanism for extracellular signaling in eukaryotes and prokaryotes2002Ingår i: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 99, nr 19, s. 12208-12213Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Epidermal growth factor receptor (EGFr) is a key mediator of cell communication during animal development and homeostasis. In Drosophila, the signaling event is commonly regulated by the polytopic membrane protein Rhomboid (RHO), which mediates the proteolytic activation of EGFr ligands, allowing the secretion of the active signal. Until very recently, the biochemical function of RHO had remained elusive. It is now believed that Drosophila RHO is the founder member of a previously undescribed family of serine proteases, and that it could be directly responsible for the unusual, intramembranous cleavage of EGFr ligands. Here we show that the function of RHO is conserved in Gram-negative bacteria. AarA, a Providencia stuartii RHO-related protein, is active in Drosophila on the fly EGFr ligands. Vice versa, Drosophila RHO-1 can effectively rescue the bacterium's ability to produce or release the signal that activates density-dependent gene regulation (or quorum sensing). This study provides the first evidence that prokaryotic and eukaryotic RHOs could have a conserved role in cell communication and that their biochemical properties could be more similar than previously anticipated.

  • 6.
    Kärblane, Kairi
    et al.
    Tallinn University of Technology, Tallinn, Estonia / Competence Centre for Cancer Research, Tallinn, Estonia .
    Gerassimenko, Jelena
    Tallinn University of Technology, Tallinn, Estonia / Competence Centre for Cancer Research, Tallinn, Estonia .
    Nigul, Lenne
    Tallinn University of Technology, Tallinn, Estonia.
    Piirsoo, Alla
    Tallinn University of Technology, Tallinn, Estonia.
    Smialowska, Agata
    Södertörns högskola, Institutionen för naturvetenskap, miljö och teknik. Karolinska Institutet.
    Vinkel, Kadri
    Tallinn University of Technology, Tallinn, Estonia .
    Kylsten, Per
    Södertörns högskola, Institutionen för naturvetenskap, miljö och teknik.
    Ekwall, Karl
    Södertörns högskola, Institutionen för naturvetenskap, miljö och teknik. Karolinska Institutet.
    Swoboda, Peter
    Karolinska Institutet.
    Truve, Erkki
    Tallinn University of Technology, Tallinn, Estonia / Competence Centre for Cancer Research, Tallinn, Estonia .
    Sarmiento, Cecilia
    Tallinn University of Technology, Tallinn, Estonia / Competence Centre for Cancer Research, Tallinn, Estonia .
    ABCE1 Is a Highly Conserved RNA Silencing Suppressor2015Ingår i: PLOS ONE, E-ISSN 1932-6203, Vol. 10, nr 2, artikel-id e0116702Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    ATP-binding cassette sub-family E member 1 (ABCE1) is a highly conserved protein among eukaryotes and archaea. Recent studies have identified ABCE1 as a ribosome-recycling factor important for translation termination in mammalian cells, yeast and also archaea. Here we report another conserved function of ABCE1. We have previously described AtRLI2, the homolog of ABCE1 in the plant Arabidopsis thaliana, as an endogenous suppressor of RNA silencing. In this study we show that this function is conserved: human ABCE1 is able to suppress RNA silencing in Nicotiana benthamiana plants, in mammalian HEK293 cells and in the worm Caenorhabditis elegans. Using co-immunoprecipitation and mass spectrometry, we found a number of potential ABCE1-interacting proteins that might support its function as an endogenous suppressor of RNA interference. The interactor candidates are associated with epigenetic regulation, transcription, RNA processing and mRNA surveillance. In addition, one of the identified proteins is translin, which together with its binding partner TRAX supports RNA interference.

  • 7.
    Markovic, Maja Pavlovic
    et al.
    Södertörns högskola, Institutionen för livsvetenskaper.
    Kylsten, Per
    Södertörns högskola, Institutionen för livsvetenskaper, Molekylärbiologi.
    Dushay, Mitchell S.
    Södertörns högskola, Institutionen för livsvetenskaper.
    Drosophila lamin mutations cause melanotic mass formation and lamellocyte differentiation2009Ingår i: Molecular Immunology, ISSN 0161-5890, E-ISSN 1872-9142, Vol. 46, nr 16, s. 3245-3250Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The fruit fly immune system is a valuable model for invertebrate and innate immunity. Cellular immune reactions in Drosophila are of great interest, especially the molecular genetic mechanisms of hemocyte differentiation and the encapsulation of foreign bodies. Here we report that changes in the lamin gene cause melanotic masses. These darkened clusters of cells result from autoimmune-like encapsulation of self-tissue, as shown by the presence in lam larvae of lamellocytes, effector hemocytes that appear in larvae following wounding or parasitization. Lamins thus affect immunity in Drosophila, and lam mutations can serve as genetic tools to dissect cellular immune signaling and effector pathways.

  • 8.
    Munoz-Alarcon, Andres
    et al.
    Södertörns högskola, Institutionen för livsvetenskaper. Karolinska Institute.
    Pavlovic, Maja
    Södertörns högskola, Institutionen för livsvetenskaper. Karolinska Institute.
    Wismar, Jasmine
    Max-Planck-Institut für Hirnforschung, Frankfurt, Germany.
    Schmitt, Bertram
    Max-Planck-Institut für Hirnforschung, Frankfurt, Germany.
    Eriksson, Maria
    Karolinska Institute.
    Kylsten, Per
    Södertörns högskola, Institutionen för livsvetenskaper.
    Dushay, Mitchell S.
    Södertörns högskola, Institutionen för livsvetenskaper. Uppsala University.
    Characterization of lamin Mutation Phenotypes in Drosophila and Comparison to Human Laminopathies2007Ingår i: PLOS ONE, E-ISSN 1932-6203, Vol. 2, nr 6, s. e532-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Lamins are intermediate filament proteins that make up the nuclear lamina, a matrix underlying the nuclear membrane in all metazoan cells that is important for nuclear form and function. Vertebrate A-type lamins are expressed in differentiating cells, while B-type lamins are expressed ubiquitously. Drosophila has two lamin genes that are expressed in A-and B-type patterns, and it is assumed that similarly expressed lamins perform similar functions. However, Drosophila and vertebrate lamins are not orthologous, and their expression patterns evolved independently. It is therefore of interest to examine the effects of mutations in lamin genes. Mutations in the mammalian lamin A/C gene cause a range of diseases, collectively called laminopathies, that include muscular dystrophies and premature aging disorders. We compared the sequences of lamin genes from different species, and we have characterized larval and adult phenotypes in Drosophila bearing mutations in the lam gene that is expressed in the B-type pattern. Larvae move less and show subtle muscle defects, and surviving lam adults are flightless and walk like aged wild-type flies, suggesting that lam phenotypes might result from neuromuscular defects, premature aging, or both. The resemblance of Drosophila lam phenotypes to human laminopathies suggests that some lamin functions may be performed by differently expressed genes in flies and mammals. Such still-unknown functions thus would not be dependent on lamin gene expression pattern, suggesting the presence of other lamin functions that are expression dependent. Our results illustrate a complex interplay between lamin gene expression and function through evolution.

  • 9.
    O'Farrell, Fergal
    et al.
    Södertörns högskola, Institutionen för livsvetenskaper. Karolinska Institute.
    Esfahani, Shiva Seyedoleslami
    Stockholms universitet.
    Engström, Ylva
    Stockholms universitet.
    Kylsten, Per
    Södertörns högskola, Institutionen för livsvetenskaper.
    Regulation of the Drosophila lin-41 homologue dappled by let-7 reveals conservation of a regulatory mechanism within the LIN-41 subclade2008Ingår i: Developmental Dynamics, ISSN 1058-8388, E-ISSN 1097-0177, Vol. 237, nr 1, s. 196-208Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Drosophila Dappled (DPLD) is a member of the RBCC/TRIM superfamily, a protein family involved in numerous diverse processes such as developmental timing and asymmetric cell divisions. DPLD belongs to the LIN-41 subclade, several members of which are micro RNA (miRNA) regulated. We re-examined the LIN-41 subclade members and their relation to other RBCC/TRIMs and dpld paralogs, and identified a new Drosophila muscle specific RBCC/TRIM: Another B-Box Affiliate, ABBA. In silico predictions of candidate miRNA regulators of dpld identified let-7 as the strongest candidate. Overexpression of dpld led to abnormal eye development, indicating that strict regulation of dpld mRNA levels is crucial for normal eye development. This phenotype was sensitive to let-7 dosage, suggesting let-7 regulation of dpld in the eye disc. A cell-based assay verified let-7 miRNA down-regulation of dpld expression by means of its 3'-untranslated region. Thus, dpld seems also to be miRNA regulated, suggesting that miRNAs represent an ancient mechanism of LIN-41 regulation.

  • 10.
    O'Farrell, Fergal
    et al.
    Södertörns högskola, Institutionen för livsvetenskaper. Karolinska Institutet.
    Kylsten, Per
    Södertörns högskola, Institutionen för livsvetenskaper.
    A mis-expression study of factors affecting Drosophila PNS cell identity2008Ingår i: Biochemical and Biophysical Research Communications - BBRC, ISSN 0006-291X, E-ISSN 1090-2104, Vol. 370, nr 4, s. 657-662Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Drosophila PNS sense organs arise from single sensory organ precursor (SOP) cells through a series of asymmetric divisions. In a mis-expression screen for factors affecting PNS development, we identified string and dappled as being important for the proper formation of adult external sensory (ES) organs. string is a G2 regulator. dappled has no described function but is implicated in tumorigenesis. The misexpression effect from string was analysed using timed over expression during adult ES-organ and, for comparison, embryonic Chorclotonal (Ch) organ formation. Surprisingly, string mis-expression prior to SOP division gave the greatest effect in both systems. In adult ES-organs, this lead to cell fate transformations producing structural cells, whilst in the embryo organs were lost, hence differences within the lineages exist. Mis-expression of dappled, lead to loss and duplications of entire organs in both systems, potentially affecting SOP specification, in addition to affecting neuronal guidance.

  • 11.
    O'Farrell, Fergal
    et al.
    Södertörns högskola, Institutionen för livsvetenskaper. Karolinska Institutet.
    Kylsten, Per
    Södertörns högskola, Institutionen för livsvetenskaper.
    Drosophila Anillin is unequally required during asymmetric cell divisions of the PNS2008Ingår i: Biochemical and Biophysical Research Communications - BBRC, ISSN 0006-291X, E-ISSN 1090-2104, Vol. 369, nr 2, s. 407-413Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    During Drosophila embryogenesis, timely and orderly asymmetric cell divisions ensure the correct number of each cell type that make up the sensory organs of the larval PNS. We report a role of scraps, Drosophila Anillin, during these divisions. Anillin, a constitutive member of the contractile ring is essential for cytokinesis in Drosophila and vertebrates. During embryogenesis we find that zygotically transcribed scraps is required specifically for the unequal cell divisions, those in which cytokinesis occurs in an "off-centred" manner, of the pIIb and pIIIb neuronal precursor cells, but not the equal cell divisions of the lineage related precursor cells. Complementation and genetic rescue studies demonstrate this effect results from zygotic scraps and leads to polyploidy, ectopic mitosis, and loss of the neuronal precursor daughter cells. The net result of which is the formation of incomplete sense organs and embryonic lethality.

  • 12.
    O'Farrell, Fergal
    et al.
    Södertörns högskola, Institutionen för livsvetenskaper. Karolinska Institutet.
    Munoz-Alarcón, Andrés
    Södertörns högskola, Institutionen för livsvetenskaper. Karolinska Institutet.
    Georgiev, Alexander
    Stockholms universitet.
    Kylsten, Per
    Södertörns högskola, Institutionen för livsvetenskaper.
    Functional Analysis of Drosophila lin-41, dappled during adult eye developmentManuskript (preprint) (Övrigt vetenskapligt)
  • 13.
    Rahman, Mokhlasur
    et al.
    Södertörns högskola, Institutionen för livsvetenskaper, Molekylärbiologi.
    Kylsten, Per
    Södertörns högskola, Institutionen för livsvetenskaper, Molekylärbiologi.
    Rhomboid-7 over-expression results in Opa1-like processing and malfunctioning mitochondria2011Ingår i: Biochemical and Biophysical Research Communications - BBRC, ISSN 0006-291X, E-ISSN 1090-2104, Vol. 414, nr 2, s. 315-320Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Rhomboid-7 (rho-7) is a mitochondrial-specific intramembranous protease. The loss-of-function mutation rho-7 results in semi-lethality, while escapers have a reduced lifespan with several neurological disorders [1]. Here we show that general, or CNS-specific expression of rho-7 can rescue the lethality of rho-7. General, or CNS-specific over-expression of rho-7 in otherwise wild-type animals caused semi-lethality, with approximately 50% of the animals escaping this lethality, developing into adults displaying a shortened life span with larval locomotory problem. On a cellular level, over-expression resulted in severe depression of ATP levels and cytochrome c oxidase subunit II mRNA levels, a lowered number of mitochondria in neurons and aggregation of mitochondria in the brain indicating mitochondrial malfunction. Over-expression of rho-7 in developing eye discs resulted in an elevated apoptotic index. In the CNS, elevated levels of rho-7 were accompanied by both isoforms of Opal-like, a dynamin-like GTPase, a mitochondrial component involved in regulating mitochondrial dynamics and function, including apoptosis. Most, but not all, of rho-7 over-expression phenotypes were suppressed by introducing a heterozygous mutation for Opal-like. Our results suggest that rho-7 and Opal-like function in a common molecular pathway affecting mitochondrial function and apoptosis in Drosophila melanogaster.

  • 14.
    Smialowska, Agata
    et al.
    Södertörns högskola, Institutionen för naturvetenskap, miljö och teknik, Biologi. Karolinska instiutet.
    Djupedal, Ingela
    Karolinska instiutet.
    Wang, Jingwen
    Karolinska instiutet.
    Kylsten, Per
    Södertörns högskola, Institutionen för naturvetenskap, miljö och teknik, Biologi.
    Swoboda, Peter
    Karolinska instiutet.
    Ekwall, Karl
    Södertörns högskola, Institutionen för naturvetenskap, miljö och teknik, Biologi. Karolinska instiutet.
    RNAi mediates post-transcriptional repression of gene expression in fission yeast Schizosaccharomyces pombe2014Ingår i: Biochemical and Biophysical Research Communications - BBRC, ISSN 0006-291X, E-ISSN 1090-2104, Vol. 444, nr 2, s. 254-259Artikel i tidskrift (Övrigt vetenskapligt)
    Abstract [en]

    RNA interference (RNAi) is a gene silencing mechanism conserved from fungi to mammals. Small interfering RNAs are products and mediators of the RNAi pathway and act as specificity factors in recruiting effector complexes. The Schizosaccharomyces pombe genome encodes one of each of the core RNAi proteins, Dicer, Argonaute and RNA-dependent RNA polymerase (dcr1, ago1, rdp1). Even though the function of RNAi in heterochromatin assembly in S. pombe is established, its role in controlling gene expression is elusive. Here, we report the identification of small RNAs mapped anti-sense to protein coding genes in fission yeast. We demonstrate that these genes are up-regulated at the protein level in RNAi mutants, while their mRNA levels are not significantly changed. We show that the repression by RNAi is not a result of heterochromatin formation. Thus, we conclude that RNAi is involved in post-transcriptional gene silencing in S. pombe.

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