BubR1 is an effector of multiple mitotic kinases that specifies kinetochore: microtubule attachments and checkpoint.
BubR1 is a critical component of the mitotic checkpoint but has also been shown to play an essential role in establishing kinetochore:microtubule attachments. BubR1 is hyperphosphorylated in mitosis and recent studies in human and Xenopus have identified 9 phosphorylation sites. Plk1-dependent phosphorylations (T792, T1008 and S676) were reported to stimulate BubR1 kinase activity, promote kinetochore microtubule attachments, monitor kinetochore tension, as well as the recruitment of Mad2 checkpoint protein to kinetochores. Plk1-independent sites (S435, S543, S670 and S1043) were also identified and some of these were found to be sensitive to the loss of microtubule attachment but not tension. Functional studies showed that phosphorylation of S670 is critical for correcting aberrant attachments. Once end-on attachments are established, dephosphorylation of S670 appeared to be important for generating tension to signal anaphase onset. The collective data when combined with early EM studies that showed BubR1 is present at both the inner and outer kinetochore plates suggest that BubR1 maybe an effector of multiple kinases that specifies its roles in microtubule attachments and checkpoint functions.
Huang
Haomin
H
Fox Chase Cancer Center, 333 Cottman Avenue, Philadelphia, PA 19111, USA. haomin.huang@fccc.edu
Yen
Timothy J
TJ
D000818:Animals; D018797:Cell Cycle Proteins / Q000378:metabolism; D006801:Humans; D018386:Kinetochores / Q000201:enzymology* / Q000648:ultrastructure; D008870:Microtubules / Q000201:enzymology*; D008938:Mitosis; D011494:Protein Kinases / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D014981:Xenopus; D000097869:Polo-Like Kinase 1
D018797:Cell Cycle Proteins; D011494:Protein Kinases; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D000097869:Polo-Like Kinase 1; C584277:BUB1 protein, human; C090464:Bub1 spindle checkpoint protein