Survivin dynamics increases at centromeres during G2/M phase transition and is regulated by microtubule-attachment and Aurora B kinase activity.
The inhibitor of apoptosis protein survivin is implicated in two key biological events: in the control of cell proliferation and in the regulation of cell lifespan. Although the details of mitotic roles of survivin are unclear, the protein appears to modulate microtubule function and might participate in regulating the spindle checkpoint. Survivin physically associates with Aurora B, a serine-threonine kinase involved in microtubule attachment to centromeres and regulation of chromosome segregation. Here we have examined the dynamics and localization of a survivin-GFP chimera using high-resolution fluorescence microscopy and photobleaching. Survivin forms a bi-partite structure at the inner centromere that undergoes significant stretching during mitosis. Photobleaching experiments revealed marked changes in rates of survivin turnover at centromeres. These were regulated by stage of the cell cycle, microtubule attachment, and Aurora B kinase activity. We hypothesize that changes in the turnover of survivin at centromeres influence the stability of kinetochore-microtubule attachment and signaling of the spindle checkpoint.
Department of Cell Biology, University of Oklahoma Health Sciences Center, 940 Stanton L. Young Boulevard, Oklahoma City, OK 73104, USA.
Victoria A
VA
Beardmore
Leena J
LJ
Ahonen
Gary J
GJ
Gorbsky
Marko J
MJ
Kallio
D000818:Animals; D064107:Aurora Kinase B; D064127:Aurora Kinases; D002455:Cell Division / Q000502:physiology; D002503:Centromere / Q000502:physiology*; D036681:Fluorescence Recovery After Photobleaching; D016195:G2 Phase / Q000502:physiology; D018816:Genes, cdc / Q000502:physiology; D006367:HeLa Cells; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins; D018374:LLC-PK1 Cells; D008869:Microtubule-Associated Proteins / Q000235:genetics* / Q000378:metabolism; D008870:Microtubules / Q000378:metabolism*; D008938:Mitosis / Q000502:physiology*; D009363:Neoplasm Proteins; D017346:Protein Serine-Threonine Kinases / Q000235:genetics* / Q000378:metabolism; D021381:Protein Transport / Q000502:physiology; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D008941:Spindle Apparatus / Q000378:metabolism*; D000077022:Survivin; D013552:Swine; D015854:Up-Regulation / Q000502:physiology
C107489:BIRC5 protein, human; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D011993:Recombinant Fusion Proteins; D000077022:Survivin; C576921:AURKB protein, human; D064107:Aurora Kinase B; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases