PMID- 10477750
OWN - NLM
STAT- MEDLINE
DCOM- 19991014
LR  - 20191023
IS  - 0021-9525 (Print)
IS  - 0021-9525 (Linking)
VI  - 146
IP  - 5
DP  - 1999 Sep 6
TI  - Human BUBR1 is a mitotic checkpoint kinase that monitors CENP-E functions at
      kinetochores and binds the cyclosome/APC.
PG  - 941-54
AB  - Human cells express two kinases that are related to the yeast mitotic checkpoint 
      kinase BUB1. hBUB1 and hBUBR1 bind to kinetochores where they are postulated to
      be components of the mitotic checkpoint that monitors kinetochore activities to
      determine if chromosomes have achieved alignment at the spindle equator
      (Jablonski, S.A., G.K.T. Chan, C.A. Cooke, W.C. Earnshaw, and T.J. Yen. 1998.
      Chromosoma. 107:386-396). In support of this, hBUB1 and the homologous mouse BUB1
      have been shown to be important for the mitotic checkpoint (Cahill, D.P., C.
      Lengauer, J. Yu, G.J. Riggins, J.K. Willson, S.D. Markowitz, K.W. Kinzler, and B.
      Vogelstein. 1998. Nature. 392:300-303; Taylor, S.S., and F. McKeon. 1997. Cell.
      89:727-735). We now demonstrate that hBUBR1 is also an essential component of the
      mitotic checkpoint. hBUBR1 is required by cells that are exposed to microtubule
      inhibitors to arrest in mitosis. Additionally, hBUBR1 is essential for normal
      mitotic progression as it prevents cells from prematurely entering anaphase. We
      establish that one of hBUBR1's checkpoint functions is to monitor kinetochore
      activities that depend on the kinetochore motor CENP-E. hBUBR1 is expressed
      throughout the cell cycle, but its kinase activity is detected after cells have
      entered mitosis. hBUBR1 kinase activity was rapidly stimulated when the spindle
      was disrupted in mitotic cells. Finally, hBUBR1 was associated with the
      cyclosome/anaphase-promoting complex (APC) in mitotically arrested cells but not 
      in interphase cells. The combined data indicate that hBUBR1 can potentially
      provide two checkpoint functions by monitoring CENP-E-dependent activities at the
      kinetochore and regulating cyclosome/APC activity.
FAU - Chan, G K
AU  - Chan GK
AD  - Institute for Cancer Research, Fox Chase Cancer Center, Philadelphia,
      Pennsylvania 19111, USA.
FAU - Jablonski, S A
AU  - Jablonski SA
FAU - Sudakin, V
AU  - Sudakin V
FAU - Hittle, J C
AU  - Hittle JC
FAU - Yen, T J
AU  - Yen TJ
LA  - eng
GR  - CA06927/CA/NCI NIH HHS/United States
GR  - GM44762/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Cell Biol
JT  - The Journal of cell biology
JID - 0375356
RN  - 0 (Bub1b protein, mouse)
RN  - 0 (Cell Cycle Proteins)
RN  - 0 (Chromosomal Proteins, Non-Histone)
RN  - 0 (centromere protein E)
RN  - EC 2.3.2.23 (Ubiquitin-Protein Ligase Complexes)
RN  - EC 2.3.2.27 (Anaphase-Promoting Complex-Cyclosome)
RN  - EC 2.3.2.27 (Ubiquitin-Protein Ligases)
RN  - EC 2.7.- (Protein Kinases)
RN  - EC 2.7.11.1 (BUB1 protein, human)
RN  - EC 2.7.11.1 (Bub1 protein, mouse)
RN  - EC 2.7.11.1 (Bub1 spindle checkpoint protein)
RN  - EC 2.7.11.1 (Protein-Serine-Threonine Kinases)
RN  - EC 6.- (Ligases)
RN  - SH1WY3R615 (Nocodazole)
SB  - IM
MH  - Anaphase/drug effects
MH  - Anaphase-Promoting Complex-Cyclosome
MH  - Apoptosis
MH  - Cell Cycle Proteins
MH  - Chromosomal Proteins, Non-Histone/*metabolism
MH  - Chromosomes, Human/drug effects/genetics/metabolism
MH  - Enzyme Activation/drug effects
MH  - Gene Expression
MH  - HeLa Cells
MH  - Humans
MH  - K562 Cells
MH  - Kinetochores/drug effects/*metabolism
MH  - Ligases/*metabolism
MH  - Metaphase/drug effects
MH  - *Mitosis/drug effects
MH  - Nocodazole/pharmacology
MH  - Phosphorylation
MH  - Precipitin Tests
MH  - Protein Binding
MH  - Protein Kinases/genetics/*metabolism
MH  - Protein-Serine-Threonine Kinases
MH  - Sequence Deletion
MH  - Spindle Apparatus/drug effects/metabolism
MH  - *Ubiquitin-Protein Ligase Complexes
MH  - Ubiquitin-Protein Ligases
PMC - PMC2169490
EDAT- 1999/09/09 00:00
MHDA- 1999/09/09 00:01
CRDT- 1999/09/09 00:00
PHST- 1999/09/09 00:00 [pubmed]
PHST- 1999/09/09 00:01 [medline]
PHST- 1999/09/09 00:00 [entrez]
AID - 10.1083/jcb.146.5.941 [doi]
PST - ppublish
SO  - J Cell Biol. 1999 Sep 6;146(5):941-54. doi: 10.1083/jcb.146.5.941.