dc.date.accessioned | 2013-03-12T12:15:44Z | |
dc.date.available | 2013-03-12T12:15:44Z | |
dc.date.issued | 2009 | en_US |
dc.date.submitted | 2009-03-11 | en_US |
dc.identifier.citation | Rogne, Marie. Regulation of PP1 and Nucleic Acid binding by AKAP149 and PNUTS . Doktoravhandling, University of Oslo, 2009 | en_US |
dc.identifier.uri | http://hdl.handle.net/10852/28127 | |
dc.description.abstract | Regulering av PP1 og Nuklein syre binding av AKAP149 og PNUTS.<br><br>
Det er estimert at 1 av 8,000 har en sykdom som konsekvens av induserte mutasjoner som påvirker mitokondrienes funksjon eller prosesser, og mitokondriell dysfunksjon blir implikert i en voksende mengde sykdommer. For eksempel kan feil i mitokondrienes fett syre oksidering føre til sykdommer som lever dysfunksjon og kardiomyopati, blant flere. Mitokondriene spiller også essensielle roller i naturlig aldring, virus infeksjon og forbrenning.<br><br>
I dette doktorarbeidet viser vi at AKAP149, som er lokalisert i mitokondriene og binder flere proteiner kjent for å være viktig i signalkaskader, er viktig for at mitokondriene skal være plassert riktig i cellene. Videre at det en konservert del av AKAP149 - KH domenet er ansvarlig for om mitokondriene er fint distribuert i nettverk eller kollapser. Dette trolig ved at AKAP149 mister evnen til binde RNA på grunn av induserte mutasjoner i KH domenet. Det er kjent at kollaps av mitokondrie nettverket kan føre til neurdegenerative sykdommer som Alzheimer, Parkinson og ASL. Spørsmålet om mutasjoner i AKAP149 som fører til kollaps av mitokondrie nettverket har noen rolle i neurodegenerative sykdommer gjenstår per dags dato. | nor |
dc.description.abstract | Transduction of an extracellular signal to intracellular effectors involves cascade of signaling events. Protein kinases and phosphatases are two major classes of effector proteins which alter the behavior of specific target proteins by phosphorylation and dephosphorylation, respectively. The phosphorylation status of proteins may contribute to define their localization, binding properties or enzymatic activity. Results presented here provide new biochemical and functional insights into two phospho-regulating proteins involved in cell cycle progression, nucleic acid binding and mitochondrial distribution.<br>
PP1 is a Ser/Thr phosphatase involved in mitosis exit and chromosome decondensation. In this study, we characterize PNUTS, a nuclear regulatory subunit of PP1. We show that recombinant PNUTS in presence of PP1 accelerates chromosome decondensation in an extract, and can promote chromosome decondensation in a buffer system. These results indicate an involvement of the PP1:PNUTS holoenzyme in chromatin decondensation.
A-kinase anchoring protein 149 (AKAP149) is localized in mitochondria and in the endoplasmic reticulum-nuclear envelope network. AKAP149 harbors in its COOH-terminal part one K-homology (KH) domain and one Tudor domain, both known to be involved in RNA binding. We show that AKAP149 self-associates in an RNA dependent manner through the KH domain. Furthermore, the KH domain of AKAP149 contains an uncharacterized PP1 binding motif in the RNA binding groove. We show that PP1 binding occurs through the PP1 binding motif in the KH domain, and that PP1 and RNA binding to this same site is mutually exclusive and controlled through a novel, phosphorylation-dependent mechanism. A collapse of the mitochondrial network is observed upon overexpression of RNA-binding deficient mutants in the KH domain of AKAP149. The results point to the importance of RNA tethering of the mitochondrial membrane by AKAP149 for mitochondrial distribution. | eng |
dc.language.iso | eng | en_US |
dc.relation.haspart | I Landsverk, H.B., Kirkhus, M., Bollen, M., Küntziger, T and Collas, P. 2005. PNUTS enhances in vitro chromosome decondensation in a PP1-dependent manner. Biochem. J. 390, 709-717 The paper is not available in DUO. The published version is available at: http://dx.doi.org/10.1042/BJ20050678 | |
dc.relation.haspart | II Rogne, M., Landsverk, H.B., Van Eynde, A., Beullens, M., Bollen, M., Collas, P and Küntziger, T. 2006. The KH domain of A-kinase Anchoring Protein 149 Mediates RNA-dependent Self-association. Biochemistry. 45(50), 14980-14989 The paper is not available in DUO. The published version is available at: http://dx.doi.org/10.1021/bi061418y | |
dc.relation.haspart | III Rogne, M., Stokka, A-J., Tasken, K., Collas, P and Küntziger, T. 2009. Mutually exclusive binding of PP1 and RNA to AKAP149 affects the mitochondrial network. Hum Mol Genet. 18(5), 978-87 The paper is not available in DUO. The published version is available at: http://dx.doi.org/10.1093/hmg/ddn425 | |
dc.relation.haspart | IV Rogne, M, Collas, P and Küntziger, T. 2009. QuickRIP – Cross-linked RNA immunoprecipitation. Manuscript. The paper is not available in DUO. | |
dc.relation.uri | http://dx.doi.org/10.1042/BJ20050678 | |
dc.relation.uri | http://dx.doi.org/10.1021/bi061418y | |
dc.relation.uri | http://dx.doi.org/10.1093/hmg/ddn425 | |
dc.title | Regulation of PP1 and Nucleic Acid binding by AKAP149 and PNUTS | en_US |
dc.type | Doctoral thesis | en_US |
dc.date.updated | 2009-04-22 | en_US |
dc.creator.author | Rogne, Marie | en_US |
dc.subject.nsi | VDP::700 | en_US |
cristin.unitcode | 130000 | en_US |
cristin.unitname | Medisinske fakultet | en_US |
dc.identifier.bibliographiccitation | info:ofi/fmt:kev:mtx:ctx&ctx_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:dissertation&rft.au=Rogne, Marie&rft.title=Regulation of PP1 and Nucleic Acid binding by AKAP149 and PNUTS &rft.inst=University of Oslo&rft.date=2009&rft.degree=Doktoravhandling | en_US |
dc.identifier.urn | URN:NBN:no-21843 | en_US |
dc.type.document | Doktoravhandling | en_US |
dc.identifier.duo | 89852 | en_US |
dc.contributor.supervisor | Philippe Collas | en_US |
dc.identifier.bibsys | 092133525 | en_US |
dc.identifier.fulltext | Fulltext https://www.duo.uio.no/bitstream/handle/10852/28127/1/745_Rogne_utenxart.pdf | |