scholarly journals Defining the role of APC in the mitotic spindle checkpoint in vivo: APC-deficient cells are resistant to Taxol

Oncogene ◽  
2010 ◽  
Vol 29 (49) ◽  
pp. 6418-6427 ◽  
Author(s):  
S Radulescu ◽  
R A Ridgway ◽  
P Appleton ◽  
K Kroboth ◽  
S Patel ◽  
...  
Keyword(s):  
Mitotic Spindle ◽  
Spindle Checkpoint ◽  
Mitotic Spindle Checkpoint

scholarly journals A Dominant Interfering Bub1 Mutant Is Insufficient To Induce or Alter Thymic Tumorigenesis In Vivo, Even in a Sensitized Genetic Background

2005 ◽  
Vol 25 (17) ◽  
pp. 7796-7802 ◽  
Author(s):  
Dale O. Cowley ◽  
Ginger W. Muse ◽  
Terry Van Dyke
Keyword(s):  
Mitotic Spindle ◽  
Genetic Background ◽  
Cultured Cells ◽  
Spindle Checkpoint ◽  
Transgenic Animals ◽  
Dominant Negative ◽  
High Level Expression ◽  
High Level

ABSTRACT Aneuploidy is a common feature of human tumors, often correlating with poor prognosis. The mitotic spindle checkpoint is thought to play a major role in aneuploidy suppression. To investigate the role of the spindle checkpoint in tumor suppression in vivo, we developed transgenic mice in which thymocytes express a dominant interfering fragment of Bub1, a kinase regulator of the spindle checkpoint. We report that, despite high-level expression of dominant-negative Bub1 (Bub1DN), a protein known to inhibit spindle checkpoint activity in cultured cells, thymocytes show no evidence of spindle checkpoint impairment. Transgenic animals also failed to show an increased predisposition to spontaneous tumors. Moreover, the Bub1DN transgene failed to alter the timing or characteristics of thymic lymphoma development in p53 heterozygous or homozygous null backgrounds, indicating that the lack of tumorigenesis is not due to suppression by p53-dependent checkpoints. These results indicate that overexpression of a Bub1 N-terminal fragment is insufficient to impair the spindle checkpoint in vivo or to drive tumorigenesis in the highly susceptible murine thymocyte system, either alone or in combination with G1 checkpoint disruption.

scholarly journals Structural activation of Mad2 in the mitotic spindle checkpoint: the two-state Mad2 model versus the Mad2 template model

2006 ◽  
Vol 173 (2) ◽  
pp. 153-157 ◽  
Author(s):  
Hongtao Yu
Keyword(s):  
Mitotic Spindle ◽  
Spindle Checkpoint ◽  
Biological Data ◽  
Anaphase Promoting Complex ◽  
Mitotic Spindle Checkpoint ◽  
Ubiquitin Ligase Activity ◽  
Large Conformational Change ◽  
A Cell ◽  
Model Versus

The inheritance of a normal assortment of chromosomes during each cell division relies on a cell-cycle surveillance system called the mitotic spindle checkpoint. The existence of sister chromatids that do not achieve proper bipolar attachment to the mitotic spindle in a cell activates this checkpoint, which inhibits the ubiquitin ligase activity of the anaphase-promoting complex or cyclosome (APC/C) and delays the onset of anaphase. The mitotic arrest deficiency 2 (Mad2) spindle checkpoint protein inhibits APC/C through binding to its mitotic-specific activator, Cdc20. Binding of Mad2 to Cdc20 involves a large conformational change of Mad2 and requires the Mad1–Mad2 interaction in vivo. Two related but distinct models of Mad1-assisted activation of Mad2, the “two-state Mad2” and the “Mad2 template” models, have been proposed. I review the recent structural, biochemical, and cell biological data on Mad2, discuss the differences between the two models, and propose experiments that test their key principles.

scholarly journals A role of the mitotic spindle checkpoint in the cellular response to DNA replication stress

2006 ◽  
Vol 99 (3) ◽  
pp. 759-769 ◽  
Author(s):  
Anette Duensing ◽  
Xiaoyi Teng ◽  
Ying Liu ◽  
Michelle Tseng ◽  
Nicole Spardy ◽  
...  
Keyword(s):  
Dna Replication ◽  
Mitotic Spindle ◽  
Cellular Response ◽  
Spindle Checkpoint ◽  
Replication Stress ◽  
Mitotic Spindle Checkpoint ◽  
Dna Replication Stress

Characterization of MAD2B and Other Mitotic Spindle Checkpoint Genes

Genomics ◽  
1999 ◽  
Vol 58 (2) ◽  
pp. 181-187 ◽  
Author(s):  
Daniel P. Cahill ◽  
Luis T. da Costa ◽  
Eleanor B. Carson-Walter ◽  
Kenneth W. Kinzler ◽  
Bert Vogelstein ◽  
...  
Keyword(s):  
Mitotic Spindle ◽  
Spindle Checkpoint ◽  
Mitotic Spindle Checkpoint ◽  
Checkpoint Genes

scholarly journals The ESCRT protein Chmp4c regulates mitotic spindle checkpoint signaling

2018 ◽  
Vol 217 (3) ◽  
pp. 861-876 ◽  
Author(s):  
Eleni Petsalaki ◽  
Maria Dandoulaki ◽  
George Zachos
Keyword(s):  
Mitotic Spindle ◽  
Spindle Checkpoint ◽  
Metaphase Plate ◽  
Membrane Remodeling ◽  
Mitotic Progression ◽  
Mitotic Spindle Checkpoint ◽  
Checkpoint Signaling ◽  
Checkpoint Proteins ◽  
Endosomal Sorting ◽  
Anaphase Onset

The mitotic spindle checkpoint delays anaphase onset in the presence of unattached kinetochores, and efficient checkpoint signaling requires kinetochore localization of the Rod–ZW10–Zwilch (RZZ) complex. In the present study, we show that human Chmp4c, a protein involved in membrane remodeling, localizes to kinetochores in prometaphase but is reduced in chromosomes aligned at the metaphase plate. Chmp4c promotes stable kinetochore–microtubule attachments and is required for proper mitotic progression, faithful chromosome alignment, and segregation. Depletion of Chmp4c diminishes localization of RZZ and Mad1-Mad2 checkpoint proteins to prometaphase kinetochores and impairs mitotic arrest when microtubules are depolymerized by nocodazole. Furthermore, Chmp4c binds to ZW10 through a small C-terminal region, and constitutive Chmp4c kinetochore targeting causes a ZW10-dependent checkpoint metaphase arrest. In addition, Chmp4c spindle functions do not require endosomal sorting complex required for transport–dependent membrane remodeling. These results show that Chmp4c regulates the mitotic spindle checkpoint by promoting localization of the RZZ complex to unattached kinetochores.

MonoallelicBUB1B mutations and defective mitotic-spindle checkpoint in seven families with premature chromatid separation (PCS) syndrome

2006 ◽  
Vol 140A (4) ◽  
pp. 358-367 ◽  
Author(s):  
Shinya Matsuura ◽  
Yoshiyuki Matsumoto ◽  
Ken-ichi Morishima ◽  
Hideki Izumi ◽  
Hiroshi Matsumoto ◽  
...  
Keyword(s):  
Mitotic Spindle ◽  
Spindle Checkpoint ◽  
Mitotic Spindle Checkpoint
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