LGALS3BP regulates centriole biogenesis and centrosome hypertrophy in cancer cells

被引:62
作者
Fogeron, Marie-Laure [1 ]
Mueller, Hannah [1 ]
Schade, Sophia [1 ]
Dreher, Felix [1 ]
Lehmann, Verena [1 ]
Kuehnel, Anne [1 ]
Scholz, Anne-Kathrin [1 ]
Kashofer, Karl [2 ]
Zerck, Alexandra [1 ]
Fauler, Beatrix [1 ]
Lurz, Rudi [1 ]
Herwig, Ralf [1 ]
Zatloukal, Kurt [2 ]
Lehrach, Hans [1 ]
Gobom, Johan [1 ]
Nordhoff, Eckhard [1 ]
Lange, Bodo M. H. [1 ,3 ]
机构
[1] Max Planck Inst Mol Genet, Dept Vertebrate Gen, D-14195 Berlin, Germany
[2] Med Univ Graz, Inst Pathol, A-8036 Graz, Austria
[3] Alacris Theranost GmbH, D-14195 Berlin, Germany
关键词
MAC-2; BINDING-PROTEIN; RING-LIKE STRUCTURES; GAMMA-TUBULIN; CYCLE; DISEASE; COMPLEX; INSTABILITY; TUMORS; IDENTIFICATION; CYTOSKELETAL;
D O I
10.1038/ncomms2517
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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 over-expressing 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.
引用
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页数:14
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