Regulation of aurora B kinase by the lipid raft protein flotillin-1.
The lipid raft protein Flotillin-1 was previously shown to be required for cell proliferation. Here we show that it is critical for the maintenance of the levels of the mitotic regulator Aurora B. Knockdown of Flotillin-1 induced aberrant mitotic events similar to those produced by Aurora B depletion and led to a marked decline in Aurora B levels and activity. Transfection of wild-type full-length Flotillin-1 or forms directed to the nucleus increased Aurora B levels and activity. Flotillin-1 interacted with Aurora B directly through its SPFH domain in a complex distinct from the chromosomal passenger protein complex, and the two proteins co-purified in nuclear, non-raft fractions. These observations are the first evidence for a function of Flotillin-1 outside of lipid rafts and suggest its critical role in the maintenance of a pool of active Aurora B.
Gómez
Valentí
V
Unitat de Recerca Biomèdica, Institut de Recerca Hospital Vall d'Hebrón, 08035 Barcelona, Spain.
Sesé
Marta
M
Santamaría
Anna
A
Martínez
Juan D
JD
Castellanos
Elisabet
E
Soler
Marta
M
Thomson
Timothy M
TM
Paciucci
Rosanna
R
D000111:Acetylcysteine / Q000031:analogs & derivatives / Q000494:pharmacology; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D064107:Aurora Kinase B; D064127:Aurora Kinases; D017675:CREST Syndrome / Q000097:blood; D002455:Cell Division; D002467:Cell Nucleus / Q000502:physiology; D017931:DNA Primers; D015536:Down-Regulation; D055785:Gene Knockdown Techniques; D006367:HeLa Cells; D006801:Humans; D020287:In Situ Nick-End Labeling; D051034:Inhibitor of Apoptosis Proteins; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D008869:Microtubule-Associated Proteins / Q000494:pharmacology; D009842:Oligopeptides / Q000494:pharmacology; D017346:Protein Serine-Threonine Kinases / Q000172:deficiency / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000737:chemistry / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000077022:Survivin; D014162:Transfection
D000900:Anti-Bacterial Agents; C107489:BIRC5 protein, human; D017931:DNA Primers; D051034:Inhibitor of Apoptosis Proteins; D008565:Membrane Proteins; D008869:Microtubule-Associated Proteins; D009842:Oligopeptides; D034741:RNA, Small Interfering; D000077022:Survivin; C106354:flotillins; C067713:lactacystin; C576921:AURKB protein, human; D064107:Aurora Kinase B; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases; D000111:Acetylcysteine; C078846:epoxomicin