scholarly journals Cells satisfy the mitotic checkpoint in Taxol, and do so faster in concentrations that stabilize syntelic attachments

2009 ◽  
Vol 186 (5) ◽  
pp. 675-684 ◽  
Author(s):  
Zhenye Yang ◽  
Alison E. Kenny ◽  
Daniela A. Brito ◽  
Conly L. Rieder
Keyword(s):  
Conceptual Framework ◽  
Drug Concentration ◽  
Mitotic Checkpoint ◽  
Cyclin B ◽  
Aurora B ◽  
Aurora B Kinase ◽  
Duration Of Mitosis ◽  
The Relationship ◽  
Do So

To determine why the duration of mitosis (DM) is less in Taxol than in nocodazole or Eg5 inhibitors we studied the relationship between Taxol concentration, the DM, and the mitotic checkpoint. We found that unlike for other spindle poisons, in Taxol the DM becomes progressively shorter as the concentration surpasses ∼0.5 µM. Studies on RPE1 and PtK2 expressing GFP/cyclin B or YFP/Mad2 revealed that cells ultimately satisfy the checkpoint in Taxol and do so faster at concentrations >0.5 µM. Inhibiting the aurora-B kinase in Taxol-treated RPE1 cells accelerates checkpoint satisfaction by stabilizing syntelic kinetochore attachments and reduces the DM to ∼1.5 h regardless of drug concentration. A similar stabilization of syntelic attachments by Taxol itself appears responsible for accelerated checkpoint satisfaction at concentrations >0.5 µM. Our results provide a novel conceptual framework for how Taxol prolongs mitosis and caution against using it in checkpoint studies. They also offer an explanation for why some cells are more sensitive to lower versus higher Taxol concentrations.

scholarly journals Untangling the contribution of Haspin and Bub1 to Aurora B function during mitosis

2020 ◽  
Vol 219 (3) ◽  
Author(s):  
Michael A. Hadders ◽  
Sanne Hindriksen ◽  
My Anh Truong ◽  
Aditya N. Mhaskar ◽  
J. Pepijn Wopken ◽  
...  
Keyword(s):  
Chromosome Segregation ◽  
Spatial Models ◽  
Mitotic Checkpoint ◽  
Aurora B ◽  
Aurora B Kinase ◽  
Chromosomal Locus

Aurora B kinase is essential for faithful chromosome segregation during mitosis. During (pro)metaphase, Aurora B is concentrated at the inner centromere by the kinases Haspin and Bub1. However, how Haspin and Bub1 collaborate to control Aurora B activity at centromeres remains unclear. Here, we show that either Haspin or Bub1 activity is sufficient to recruit Aurora B to a distinct chromosomal locus. Moreover, we identified a small, Bub1 kinase–dependent Aurora B pool that supported faithful chromosome segregation in otherwise unchallenged cells. Joined inhibition of Haspin and Bub1 activities fully abolished Aurora B accumulation at centromeres. While this impaired the correction of erroneous KT–MT attachments, it did not compromise the mitotic checkpoint, nor the phosphorylation of the Aurora B kinetochore substrates Hec1, Dsn1, and Knl1. This suggests that Aurora B substrates at the kinetochore are not phosphorylated by centromere-localized pools of Aurora B, and calls for a reevaluation of the current spatial models for how tension affects Aurora B–dependent kinetochore phosphorylation.

scholarly journals Aurora B phosphorylates Bub1 to promote spindle assembly checkpoint signaling

2021 ◽  
Author(s):  
Babhrubahan Roy ◽  
Simon J. Y. Han ◽  
Adrienne N. Fontan ◽  
Ajit P. Joglekar
Keyword(s):  
Error Correction ◽  
Spindle Assembly Checkpoint ◽  
Spindle Assembly ◽  
Mitotic Checkpoint ◽  
Aurora B ◽  
Aurora B Kinase ◽  
Checkpoint Signaling ◽  
Binding Interface ◽  
Anaphase Onset ◽  
Error Correction Mechanism

SummaryAccurate chromosome segregation during cell division requires amphitelic attachment of each chromosome to the spindle apparatus. This is ensured by the Spindle Assembly Checkpoint (SAC) [1], which delays anaphase onset in response to unattached chromosomes, and an error correction mechanism, which eliminates syntelic chromosome attachments [2]. The SAC is activated by the Mps1 kinase. Mps1 sequentially phosphorylates the kinetochore protein Spc105/KNL1 to license the recruitment of several signaling proteins including Bub1. These proteins produce the Mitotic Checkpoint Complex (MCC), which delays anaphase onset [3-8]. The error correction mechanism is regulated by the Aurora B kinase, which phosphorylates the microtubule-binding interface of the kinetochore. Aurora B is also known to promote SAC signaling indirectly [9-12]. Here we present evidence that Aurora B kinase activity directly promotes MCC production in budding yeast and human cells. Using the ectopic SAC activation (eSAC) system, we find that the conditional dimerization of Aurora B (or an Aurora B recruitment domain) with either Bub1 or Mad1, but not the ‘MELT’ motifs in Spc105/KNL1, leads to a SAC-mediated mitotic arrest [13-16]. Importantly, ectopic MCC production driven by Aurora B requires the ability of Bub1 to bind both Mad1 and Cdc20. These and other data show that Aurora B cooperates with Bub1 to promote MCC production only after Mps1 licenses Bub1 recruitment to the kinetochore. This direct involvement of Aurora B in SAC signaling is likely important for syntelically attached sister kinetochores that must delay anaphase onset in spite of reduced Mps1 activity due to their end-on microtubule attachment.

Home, Sweet Home: Negotiating Intimacy in Brazilian Elitist Closed Condominiums

2020 ◽  
Vol 9 (1) ◽  
pp. 374-395
Author(s):  
Rafael Ignacio Estrada Mejia ◽  
Carla Guerrón Guerron Montero
Keyword(s):  
Collective Mode ◽  
Living Arrangement ◽  
Public Life ◽  
Ethnographic Research ◽  
Social Distinction ◽  
History Of ◽  
Collective Production ◽  
The Relationship ◽  
Do So

This article aims to decrease the cultural invisibility of the wealthy by exploring the Brazilian emergent elites and their preferred living arrangement: elitist closed condominiums (BECCs) from a micropolitical perspective.  We answer the question: What is the relationship between intimacy and subjectivity that is produced in the collective mode of existence of BECCs? To do so, we trace the history of the elite home, from the master’s house (casa grande) to contemporary closed condominiums. Following, we discuss the features of closed condominiums as spaces of segregation, fragmentation and social distinction, characterized by minimal public life and an internalized sociability. Finally, based on ethnographic research conducted in the mid-size city of Londrina (state of Paraná) between 2015 and 2017, we concentrate on four members of the emergent elite who live in BECCs, addressing their collective production of subjectivity. 

The Role of the Judiciary and Its Relationship to the Convention on the Rights of Persons with Disabilities

2018 ◽  
Author(s):  
Lisa Waddington
Keyword(s):  
Legal System ◽  
Amicus Curiae ◽  
Persons With Disabilities ◽  
Legal Duty ◽  
The Relationship ◽  
Do So

This chapter examines the role of the judiciary with regard to the Convention on the Rights of Persons with Disabilities (CRPD). It considers the relationship which the judiciary have or appear to perceive themselves as having with the CRPD and explores some of the factors seemingly prompting courts to refer to it. The first section reflects on: whether judges are able to choose to refer to the Convention or have a legal duty to do so; the significance of the fact that the CRPD is international law; and whether judges appear to see themselves merely as domestic actors, or as agents or trustees of the CRPD. The second section explores whether judges are referring to the CRPD in response to arguments raised before the court or doing so of their own volition. Also considered are the relevance of amicus curiae interventions; reasons for referral related to the domestic legal system; and the role of particularly engaged individuals.

Protecting Natural Resources

2018 ◽  
Author(s):  
Jérémie Gilbert
Keyword(s):  
Climate Change ◽  
Human Rights ◽  
Natural Resources ◽  
Environmental Law ◽  
Legal Framework ◽  
Human Rights Law ◽  
International Environmental Law ◽  
Conservation Of Natural Resources ◽  
The Relationship ◽  
Do So

This chapter focuses on the connection between the international legal framework governing the conservation of natural resources and human rights law. The objective is to examine the potential synergies between international environmental law and human rights when it comes to the protection of natural resources. To do so, it concentrates on three main areas of potential convergence. It first focuses on the pollution of natural resources and analyses how human rights law offers a potential platform to seek remedies for the victims of pollution. It next concentrates on the conservation of natural resources, particularly on the interconnection between protected areas, biodiversity, and human rights law. Finally, it examines the relationship between climate change and human rights law, focusing on the role that human rights law can play in the development of the current climate change adaptation and mitigation frameworks.

Cultural Labour

2019 ◽  
Author(s):  
Brahma Prakash
Keyword(s):  
Conceptual Framework ◽  
Performance Studies ◽  
Life Experience ◽  
Social Hierarchies ◽  
Folk Performance ◽  
And Performance ◽  
The Relationship

Folk performances reflect the life-worlds of a vast section of subaltern communities in India. What is the philosophy that drives these performances, the vision that enables as well as enslaves these communities to present what they feel, think, imagine, and want to see? Can such performances challenge social hierarchies and ensure justice in a caste-ridden society? In Cultural Labour, the author studies bhuiyan puja (land worship), bidesia (theatre of migrant labourers), Reshma-Chuharmal (Dalit ballads), dugola (singing duels) from Bihar, and the songs and performances of Gaddar, who was associated with Jana Natya Mandali, Telangana: he examines various ways in which meanings and behaviour are engendered in communities through rituals, theatre, and enactments. Focusing on various motifs of landscape, materiality, and performance, the author looks at the relationship between culture and labour in its immediate contexts. Based on an extensive ethnography and the author’s own life experience as a member of such a community, the book offers a new conceptual framework to understand the politics and aesthetics of folk performance in the light of contemporary theories of theatre and performance studies.

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