Faculty Opinions recommendation of Cyclin B degradation leads to NuMA release from dynein/dynactin and from spindle poles.

2004 ◽  
Author(s):  
Rebecca Heald
Keyword(s):  
Cyclin B ◽  
Spindle Poles

scholarly journals Cells protect chromosome-microtubule attachments, independent of biorientation, using an Astrin-PP1 and CyclinB-CDK1 feedback loop

2020 ◽  
Author(s):  
Duccio Conti ◽  
Xinhong Song ◽  
Roshan L. Shrestha ◽  
Dominique Braun ◽  
Viji M Draviam
Keyword(s):  
Chromosomal Instability ◽  
Feedback Loop ◽  
Cyclin B ◽  
Macromolecular Structure ◽  
Aurora B ◽  
Unique Role ◽  
Spindle Poles ◽  
Microtubule Attachment ◽  
Segregation Of Chromosomes

Defects in chromosome-microtubule attachment can cause chromosomal instability, associated with infertility and aggressive cancers. Chromosome-microtubule attachment is mediated by a large macromolecular structure, the kinetochore. Kinetochore pairs are bioriented and pulled by microtubules from opposing spindle poles to ensure the equal segregation of chromosomes. Kinetochore-microtubule attachments lacking opposing-pull are detached by Aurora-B/Ipl1; yet, how mono-oriented attachments that are a prerequisite for biorientation, but lacking opposing-pull are spared is unclear. Using an RNAi-mediated screen, we uncover a unique role for the Astrin-SKAP complex in protecting mono-oriented attachments. We provide the first evidence for how a microtubule-end associated protein senses outer-kinetochore changes specific to end-on attachments and assembles into an outer kinetochore crescent to stabilise mature attachments. We find that Astrin-PP1 and Cyclin-B-CDK1 activities counteract each other to preserve mono-oriented attachments. Thus, cells are not only surveying chromosome-microtubule attachment errors, but they are also actively sensing and stabilising mature attachments independent of biorientation.

Mitotic motors and chromosome segregation: the mechanism of anaphase B

2011 ◽  
Vol 39 (5) ◽  
pp. 1149-1153 ◽  
Author(s):  
Ingrid Brust-Mascher ◽  
Jonathan M. Scholey
Keyword(s):  
Chromosome Segregation ◽  
Cyclin B ◽  
Spindle Poles ◽  
Mitotic Motors ◽  
Balance Of Forces ◽  
Spindle Elongation ◽  
Anaphase B ◽  
Relationship Of ◽  
The Relationship ◽  
Acting In Concert

Anaphase B spindle elongation plays an important role in chromosome segregation. In the present paper, we discuss our model for anaphase B in Drosophila syncytial embryos, in which spindle elongation depends on an ip (interpolar) MT (microtubule) sliding filament mechanism generated by homotetrameric kinesin-5 motors acting in concert with poleward ipMT flux, which acts as an ‘on/off’ switch. Specifically, the pre-anaphase B spindle is maintained at a steady-state length by the balance between ipMT sliding and ipMT depolymerization at spindle poles, producing poleward flux. Cyclin B degradation at anaphase B onset triggers: (i) an MT catastrophe gradient causing ipMT plus ends to invade the overlap zone where ipMT sliding forces are generated; and (ii) the inhibition of ipMT minus-end depolymerization so flux is turned ‘off’, tipping the balance of forces to allow outward ipMT sliding to push apart the spindle poles. We briefly comment on the relationship of this model to anaphase B in other systems.

scholarly journals CDK-1 inhibits meiotic spindle shortening and dynein-dependent spindle rotation in C. elegans

2011 ◽  
Vol 193 (7) ◽  
pp. 1229-1244 ◽  
Author(s):  
Marina L. Ellefson ◽  
Francis J. McNally
Keyword(s):  
Polar Body ◽  
Spindle Pole ◽  
Cyclin B ◽  
Meiotic Spindle ◽  
Anaphase Promoting Complex ◽  
C Elegans ◽  
Perpendicular Orientation ◽  
Spindle Poles ◽  
Spindle Rotation ◽  
Chromosome Separation

In animals, the female meiotic spindle is positioned at the egg cortex in a perpendicular orientation to facilitate the disposal of half of the chromosomes into a polar body. In Caenorhabditis elegans, the metaphase spindle lies parallel to the cortex, dynein is dispersed on the spindle, and the dynein activators ASPM-1 and LIN-5 are concentrated at spindle poles. Anaphase-promoting complex (APC) activation results in dynein accumulation at spindle poles and dynein-dependent rotation of one spindle pole to the cortex, resulting in perpendicular orientation. To test whether the APC initiates spindle rotation through cyclin B–CDK-1 inactivation, separase activation, or degradation of an unknown dynein inhibitor, CDK-1 was inhibited with purvalanol A in metaphase-I–arrested, APC-depleted embryos. CDK-1 inhibition resulted in the accumulation of dynein at spindle poles and dynein-dependent spindle rotation without chromosome separation. These results suggest that CDK-1 blocks rotation by inhibiting dynein association with microtubules and with LIN-5–ASPM-1 at meiotic spindle poles and that the APC promotes spindle rotation by inhibiting CDK-1.

scholarly journals Quantitative analysis of an anaphase B switch: predicted role for a microtubule catastrophe gradient

2007 ◽  
Vol 177 (6) ◽  
pp. 995-1004 ◽  
Author(s):  
Dhanya K. Cheerambathur ◽  
Gul Civelekoglu-Scholey ◽  
Ingrid Brust-Mascher ◽  
Patrizia Sommi ◽  
Alex Mogilner ◽  
...  
Keyword(s):  
Fluorescence Recovery After Photobleaching ◽  
Complete Recovery ◽  
Cyclin B ◽  
Spatial Gradient ◽  
Spindle Poles ◽  
Spindle Elongation ◽  
Anaphase B ◽  
Mechanical Switch ◽  
Lower Recovery ◽  
Drosophila Embryos

Anaphase B in Drosophila embryos is initiated by the inhibition of microtubule (MT) depolymerization at spindle poles, which allows outwardly sliding interpolar (ip) MTs to drive pole–pole separation. Using fluorescence recovery after photobleaching, we observed that MTs throughout the preanaphase B spindle are very dynamic and display complete recovery of fluorescence, but during anaphase B, MTs proximal to the poles stabilize and therefore display lower recovery than those elsewhere. Fluorescence microscopy of the MT tip tracker EB1 revealed that growing MT plus ends localize throughout the preanaphase B spindle but concentrate in the overlap region of interpolar MTs (ipMTs) at anaphase B onset. None of these changes occurred in the presence of nondegradable cyclin B. Modeling suggests that they depend on the establishment of a spatial gradient of MT plus-end catastrophe frequencies, decreasing toward the equator. The resulting redistribution of ipMT plus ends to the overlap zone, together with the suppression of minus-end depolymerization at the poles, could constitute a mechanical switch that initiates spindle elongation.

scholarly journals Cyclin B degradation leads to NuMA release from dynein/dynactin and from spindle poles

EMBO Reports ◽  
2004 ◽  
Vol 5 (1) ◽  
pp. 97-103 ◽  
Author(s):  
Katja Gehmlich ◽  
Laurence Haren ◽  
Andreas Merdes
Keyword(s):  
Cyclin B ◽  
Spindle Poles

scholarly journals Katanin Is Responsible for the M-Phase Microtubule-severing Activity in Xenopus Eggs

1998 ◽  
Vol 9 (7) ◽  
pp. 1847-1861 ◽  
Author(s):  
Francis J. McNally ◽  
Susan Thomas
Keyword(s):  
Cell Cycle ◽  
Human Fibroblasts ◽  
Cyclin B ◽  
Microtubule Severing ◽  
Spindle Poles ◽  
M Phase ◽  
Egg Extracts ◽  
Dynamic Structures ◽  
Cycle Dependent ◽  
Xenopus Egg Extracts

Microtubules are dynamic structures whose proper rearrangement during the cell cycle is essential for the positioning of membranes during interphase and for chromosome segregation during mitosis. The previous discovery of a cyclin B/cdc2-activated microtubule-severing activity in M-phase Xenopus egg extracts suggested that a microtubule-severing protein might play an important role in cell cycle-dependent changes in microtubule dynamics and organization. However, the isolation of three different microtubule-severing proteins, p56, EF1α, and katanin, has only confused the issue because none of these proteins is directly activated by cyclin B/cdc2. Here we use immunodepletion with antibodies specific for a vertebrate katanin homologue to demonstrate that katanin is responsible for the majority of M-phase severing activity inXenopus eggs. This result suggests that katanin is responsible for changes in microtubules occurring at mitosis. Immunofluorescence analysis demonstrated that katanin is concentrated at a microtubule-dependent structure at mitotic spindle poles inXenopus A6 cells and in human fibroblasts, suggesting a specific role in microtubule disassembly at spindle poles. Surprisingly, katanin was also found in adult mouse brain, indicating that katanin may have other functions distinct from its mitotic role.

scholarly journals Plk1 Regulates Activation of the Anaphase Promoting Complex by Phosphorylating and Triggering SCFβTrCP-dependent Destruction of the APC Inhibitor Emi1

2004 ◽  
Vol 15 (12) ◽  
pp. 5623-5634 ◽  
Author(s):  
David V. Hansen ◽  
Alexander V. Loktev ◽  
Kenneth H. Ban ◽  
Peter K. Jackson
Keyword(s):  
Ubiquitin Ligase ◽  
Mitotic Spindle ◽  
Cyclin B ◽  
Anaphase Promoting Complex ◽  
Downstream Targets ◽  
Spindle Poles ◽  
Data Support

Progression through mitosis requires activation of cyclin B/Cdk1 and its downstream targets, including Polo-like kinase and the anaphase-promoting complex (APC), the ubiquitin ligase directing degradation of cyclins A and B. Recent evidence shows that APC activation requires destruction of the APC inhibitor Emi1. In prophase, phosphorylation of Emi1 generates a D-pS-G-X-X-pS degron to recruit the SCFβTrCP ubiquitin ligase, causing Emi1 destruction and allowing progression beyond prometaphase, but the kinases directing this phosphorylation remain undefined. We show here that the polo-like kinase Plk1 is strictly required for Emi1 destruction and that overexpression of Plk1 is sufficient to trigger Emi1 destruction. Plk1 stimulates Emi1 phosphorylation, βTrCP binding, and ubiquitination in vitro and cyclin B/Cdk1 enhances these effects. Plk1 binds to Emi1 in mitosis and the two proteins colocalize on the mitotic spindle poles, suggesting that Plk1 may spatially control Emi1 destruction. These data support the hypothesis that Plk1 activates the APC by directing the SCF-dependent destruction of Emi1 in prophase.

scholarly journals WARTS tumor suppressor is phosphorylated by Cdc2/cyclin B at spindle poles during mitosis

FEBS Letters ◽  
2002 ◽  
Vol 529 (2-3) ◽  
pp. 319-324 ◽  
Author(s):  
Tetsuro Morisaki ◽  
Toru Hirota ◽  
Shin-ichi Iida ◽  
Tomotoshi Marumoto ◽  
Toshihiro Hara ◽  
...  
Keyword(s):  
Tumor Suppressor ◽  
Cyclin B ◽  
Spindle Poles

scholarly journals Control of division and microtubule dynamics in Chlamydomonas by cyclin B/CDKB1 and the anaphase-promoting complex

2021 ◽  
Author(s):  
Frederick Cross ◽  
Kresti Pecani ◽  
Kristi Lieberman ◽  
Natsumi Tajima-Shirasaki ◽  
Masayuki Onishi
Keyword(s):  
Time Lapse ◽  
Microtubule Dynamics ◽  
Cyclin B ◽  
Live Cells ◽  
Cyclin Dependent Kinase ◽  
Anaphase Promoting Complex ◽  
Mitotic Progression ◽  
Time Lapse Microscopy ◽  
Spindle Poles ◽  
Multiple Fission

In yeast and animals, cyclin B binds and activates the cyclin-dependent kinase ('CDK') CDK1 to drive entry into mitosis. We show that CYCB1, the sole cyclin B in Chlamydomonas, activates the plant-specific CDKB1 rather than the CDK1 ortholog CDKA1. Time-lapse microscopy shows that CYCB1 is synthesized before each division in the multiple fission cycle, then is rapidly degraded 3-5 minutes before division occurs. CYCB1 degradation is dependent on the anaphase-promoting complex (APC). Like CYCB1, CDKB1 is not synthesized until late G1; however, CDKB1 is not degraded with each division within the multiple fission cycle. The microtubule plus-end-binding protein EB1 labeled with mNeonGreen (EB1-NG) allowed detection of mitotic events in live cells. The earliest detectable step in mitosis, splitting of polar EB1-NG signal into two foci, likely associated with future spindle poles, was dependent on CYCB1. CYCB1-GFP localized close to these foci immediately before spindle formation. Spindle breakdown, cleavage furrow formation and accumulation of EB1 in the furrow were dependent on the APC. In interphase, rapidly growing microtubules are marked by 'comets' of EB1; comets are absent in the absence of APC function. Thus CYCB1/CDKB1 and the APC mitosis modulate microtubule dynamics while regulating mitotic progression.

Sign in / Sign up

Export Citation Format

Share Document