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  Dynamic targeting of microtubules by TPPP/p25 affects cell survival.

Lehotzky, A., Tirián, L., Tökési, N., Lenart, P., Szabó, B., Kovács, J., et al. (2004). Dynamic targeting of microtubules by TPPP/p25 affects cell survival. Journal of Cell Science, 117, 6249-6259. doi:10.1242/jcs.01550.

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Lehotzky, A., Autor
Tirián, L., Autor
Tökési, N., Autor
Lenart, P.1, Autor           
Szabó, B., Autor
Kovács, J., Autor
Ovádi, J., Autor
Affiliations:
1Research Group of Cytoskeletal Dynamics in Oocytes, MPI for Biophysical Chemistry, Max Planck Society, ou_2640691              

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 Zusammenfassung: Recently we identified TPPP/p25 (tubulin polymerization promoting protein/p25) as a brain-specific unstructured protein that induced aberrant microtubule assemblies and ultrastructure in vitro and as a new marker for Parkinson's disease and other synucleopathies. In this paper the structural and functional consequences of TPPP/p25 are characterized to elucidate the relationship between the in vitro and the pathological phenomena. We show that at low expression levels EGFP-TPPP/p25 specifically colocalizes with the microtubule network of HeLa and NRK cells. We found that the colocalization was dynamic (tg=5 seconds by fluorescence recovery after photobleaching) and changed during the phases of mitosis. Time-lapse and immunofluorescence experiments revealed that high levels of EGFP-TPPP/p25 inhibited cell division and promoted cell death. At high expression levels or in the presence of proteosome inhibitor, green fusion protein accumulated around centrosomes forming an aggresome-like structure protruding into the nucleus or a filamentous cage of microtubules surrounding the nucleus. These structures showed high resistance to vinblastin. We propose that a potential function of TPPP/p25 is the stabilization of physiological microtubular ultrastructures, however, its upregulation may directly or indirectly initiate the formation of aberrant protein aggregates such as pathological inclusions.

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Sprache(n): eng - English
 Datum: 2004
 Publikationsstatus: Erschienen
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 Ort, Verlag, Ausgabe: -
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 Art der Begutachtung: Expertenbegutachtung
 Identifikatoren: DOI: 10.1242/jcs.01550
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Titel: Journal of Cell Science
Genre der Quelle: Zeitschrift
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Ort, Verlag, Ausgabe: -
Seiten: - Band / Heft: 117 Artikelnummer: - Start- / Endseite: 6249 - 6259 Identifikator: -