Topic
BUB3
About: BUB3 is a research topic. Over the lifetime, 214 publications have been published within this topic receiving 23497 citations. The topic is also known as: BUB3L & hBUB3.
Papers published on a yearly basis
Papers
TL;DR: The data reveal that molecules in or near the unattached kinetochore of a monooriented PtK1 chromosome inhibit the metaphase-anaphase transition.
Abstract: During mitosis in Ptk1 cells anaphase is not initiated until, on average, 23 +/- 1 min after the last monooriented chromosome acquires a bipolar attachment to the spindle--an event that may require 3 h (Rieder, C. L., A. Schultz, R. W. Cole, and G. Sluder. 1994. J. Cell Biol. 127:1301-1310). To determine the nature of this cell-cycle checkpoint signal, and its site of production, we followed PtK1 cells by video microscopy prior to and after destroying specific chromosomal regions by laser irradiation. The checkpoint was relieved, and cells entered anaphase, 17 +/- 1 min after the centromere (and both of its associated sister kinetochores) was destroyed on the last monooriented chromosome. Thus, the checkpoint mechanism monitors an inhibitor of anaphase produced in the centromere of monooriented chromosomes. Next, in the presence of one monooriented chromosome, we destroyed one kinetochore on a bioriented chromosome to create a second monooriented chromosome lacking an unattached kinetochore. Under this condition anaphase began in the presence of the experimentally created monooriented chromosome 24 +/- 1.5 min after the nonirradiated monooriented chromosome bioriented. This result reveals that the checkpoint signal is not generated by the attached kinetochore of a monooriented chromosome or throughout the centromere volume. Finally, we selectively destroyed the unattached kinetochore on the last monooriented chromosome. Under this condition cells entered anaphase 20 +/- 2.5 min after the operation, without congressing the irradiated chromosome. Correlative light microscopy/elctron microscopy of these cells in anaphase confirmed the absence of a kinetochore on the unattached chromatid. Together, our data reveal that molecules in or near the unattached kinetochore of a monooriented PtK1 chromosome inhibit the metaphase-anaphase transition.
813 citations
TL;DR: It is shown that the checkpoint-mediated cell cycle arrest involves hMAD2 receiving an upstream signal to inhibit activation of APC, and a change in hM AD2 structure may play a role in transducing the checkpoint signal.
Abstract: The spindle assembly checkpoint mechanism delays anaphase initiation until all chromosomes are aligned at the metaphase plate. Activation of the anaphase-promoting complex (APC) by binding of CDC20 and CDH1 is required for exit from mitosis, and APC has been implicated as a target for the checkpoint intervention. We show that the human checkpoint protein hMAD2 prevents activation of APC by forming a hMAD2-CDC20-APC complex. When injected into Xenopus embryos, hMAD2 arrests cells at mitosis with an inactive APC. The recombinant hMAD2 protein exists in two-folded states: a tetramer and a monomer. Both the tetramer and the monomer bind to CDC20, but only the tetramer inhibits activation of APC and blocks cell cycle progression. Thus, hMAD2 binding is not sufficient for inhibition, and a change in hMAD2 structure may play a role in transducing the checkpoint signal. There are at least three different forms of mitotic APC that can be detected in vivo: an inactive hMAD2-CDC20-APC ternary complex present at metaphase, a CDC20-APC binary complex active in degrading specific substrates at anaphase, and a CDH1-APC complex active later in mitosis and in G1. We conclude that the checkpoint-mediated cell cycle arrest involves hMAD2 receiving an upstream signal to inhibit activation of APC.
651 citations
TL;DR: The "Mad2 template" model predicts a mechanism for cytosolic propagation of the spindle checkpoint signal away from kinetochores and proposes that closed Mad2 bound to Mad1 represents a template for the conversion of open Mad2 into closed Mad 2 bound to Cdc20.
489 citations
TL;DR: The mitotic checkpoint blocks the activation of the anaphase-promoting complex (APC) until all sister chromatids have achieved bipolar attachment to the spindle, and the ability of BubR1 to inhibit APC may be regulated by kinetochore tension or occupancy.
468 citations
TL;DR: Relief of dependence appears to be a result of deregulation of ubiquitin-dependent proteolysis mediated by the anaphase-promoting complex.
Abstract: Mad2 is a component of the spindle checkpoint, which delays the onset of anaphase until all chromosomes are attached to the spindle. Mad2 formed a complex with Slp1, a WD (tryptophan-aspartic acid)-repeat protein essential for the onset of anaphase. When the physical interaction between the two proteins was disrupted, the spindle checkpoint was no longer functional. Post-anaphase events such as chromosome decondensation and the next round of DNA replication were not delayed even when the spindle assembly was incomplete. This relief of dependence appears to be a result of deregulation of ubiquitin-dependent proteolysis mediated by the anaphase-promoting complex.
417 citations
Related Topics (5)
Performance Metrics
| Year | Papers |
|---|---|
| 2021 | 5 |
| 2020 | 6 |
| 2019 | 5 |
| 2018 | 7 |
| 2017 | 6 |
| 2016 | 10 |