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Fogeron, ML; Muller, H; Schade, S; Dreher, F; Lehmann, V; Kuhnel, A; Scholz, AK; Kashofer, K; Zerck, A; Fauler, B; Lurz, R; Herwig, R; Zatloukal, K; Lehrach, H; Gobom, J; Nordhoff, E; Lange, BMH; .
LGALS3BP regulates centriole biogenesis and centrosome hypertrophy in cancer cells.
NAT COMMUN. 2013; 4(2): 1531-1531.
Doi: 10.1038/ncomms2517
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- Co-Autor*innen der Med Uni Graz
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Kashofer Karl
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Zatloukal Kurt
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- Abstract:
- Centrosome morphology and number are frequently deregulated in cancer cells. Here, to identify factors that are functionally relevant for centrosome abnormalities in cancer cells, we established a protein-interaction network around 23 centrosomal and cell-cycle regulatory proteins, selecting the interacting proteins that are deregulated in cancer for further studies. One of these components, LGALS3BP, is a centriole- and basal body-associated protein with a dual role, triggering centrosome hypertrophy when overexpressed and causing accumulation of centriolar substructures when downregulated. The cancer cell line SK-BR-3 that overexpresses LGALS3BP exhibits hypertrophic centrosomes, whereas in seminoma tissues with low expression of LGALS3BP, supernumerary centriole-like structures are present. Centrosome hypertrophy is reversed by depleting LGALS3BP in cells endogenously overexpressing this protein, supporting a direct role in centrosome aberration. We propose that LGALS3BP suppresses assembly of centriolar substructures, and when depleted, causes accumulation of centriolar complexes comprising CPAP, acetylated tubulin and centrin.
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Animals -
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Antigens, Neoplasm - genetics Antigens, Neoplasm - metabolism
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Carrier Proteins - genetics Carrier Proteins - metabolism
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Cell Line, Tumor -
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Centrioles - metabolism Centrioles - pathology Centrioles - ultrastructure
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Chromatography, Affinity -
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Extracellular Matrix Proteins - metabolism
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Gene Expression Regulation, Neoplastic -
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Gene Knockdown Techniques -
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Glycoproteins - genetics Glycoproteins - metabolism
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HEK293 Cells -
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Humans -
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Hypertrophy -
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Male -
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Microtubules - metabolism Microtubules - ultrastructure
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Mitotic Spindle Apparatus - metabolism Mitotic Spindle Apparatus - ultrastructure
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Neoplasms - genetics Neoplasms - metabolism Neoplasms - pathology
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Protein Interaction Maps -
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Protein Transport -
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Protein-Serine-Threonine Kinases - metabolism
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RNA, Small Interfering - metabolism
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Rats -
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Rats, Sprague-Dawley -
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Seminoma - genetics Seminoma - pathology
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Tumor Markers, Biological - genetics Tumor Markers, Biological - metabolism