Integrin-linked kinase localizes to the centrosome and regulates mitotic spindle organization.
Integrin-linked kinase (ILK) is a serine-threonine kinase and scaffold protein with well defined roles in focal adhesions in integrin-mediated cell adhesion, spreading, migration, and signaling. Using mass spectrometry-based proteomic approaches, we identify centrosomal and mitotic spindle proteins as interactors of ILK. alpha- and beta-tubulin, ch-TOG (XMAP215), and RUVBL1 associate with ILK and colocalize with it to mitotic centrosomes. Inhibition of ILK activity or expression induces profound apoptosis-independent defects in the organization of the mitotic spindle and DNA segregation. ILK fails to localize to the centrosomes of abnormal spindles in RUVBL1-depleted cells. Additionally, depletion of ILK expression or inhibition of its activity inhibits Aurora A-TACC3/ch-TOG interactions, which are essential for spindle pole organization and mitosis. These data demonstrate a critical and unexpected function for ILK in the organization of centrosomal protein complexes during mitotic spindle assembly and DNA segregation.
Fielding
Andrew B
AB
Department of Cancer Genetics, British Columbia Cancer Research Centre of the British Columbia Cancer Agency, Vancouver, BC, Canada.
Dobreva
Iveta
I
McDonald
Paul C
PC
Foster
Leonard J
LJ
Dedhar
Shoukat
S
D000074183:ATPases Associated with Diverse Cellular Activities; D064127:Aurora Kinases; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D018385:Centrosome / Q000201:enzymology* / Q000648:ultrastructure; D020090:Chromosome Segregation / Q000235:genetics*; D004265:DNA Helicases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D015536:Down-Regulation / Q000235:genetics; D006367:HeLa Cells; D006801:Humans; D013058:Mass Spectrometry; D008869:Microtubule-Associated Proteins / Q000737:chemistry / Q000378:metabolism; D008938:Mitosis / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D017434:Protein Structure, Tertiary / Q000235:genetics; D008941:Spindle Apparatus / Q000201:enzymology* / Q000235:genetics / Q000648:ultrastructure; D014404:Tubulin / Q000737:chemistry / Q000378:metabolism; D000099200:Scaffold Protein ILK
D000074183:ATPases Associated with Diverse Cellular Activities; D064127:Aurora Kinases; D002352:Carrier Proteins; D004265:DNA Helicases; D008869:Microtubule-Associated Proteins; D009687:Nuclear Proteins; D017346:Protein Serine-Threonine Kinases; D014404:Tubulin; D000099200:Scaffold Protein ILK; C454180:CKAP5 protein, human; C486549:RUVBL1 protein, human