scholarly journals Cyclin-dependent kinase 2 is dispensable for normal centrosome duplication but required for oncogene-induced centrosome overduplication

Oncogene ◽  
2006 ◽  
Vol 25 (20) ◽  
pp. 2943-2949 ◽  
Author(s):  
A Duensing ◽  
Y Liu ◽  
M Tseng ◽  
M Malumbres ◽  
M Barbacid ◽  
...  
2001 ◽  
Vol 276 (24) ◽  
pp. 21529-21537 ◽  
Author(s):  
Yukari Tokuyama ◽  
Henning F. Horn ◽  
Kenji Kawamura ◽  
Pheruza Tarapore ◽  
Kenji Fukasawa

1999 ◽  
Vol 9 (8) ◽  
pp. 429-432 ◽  
Author(s):  
Yutaka Matsumoto ◽  
Ken Hayashi ◽  
Eisuke Nishida

2007 ◽  
Vol 18 (11) ◽  
pp. 4457-4469 ◽  
Author(s):  
Christopher Kasbek ◽  
Ching-Hui Yang ◽  
Adlina Mohd Yusof ◽  
Heather M. Chapman ◽  
Mark Winey ◽  
...  

Supernumerary centrosomes promote the assembly of abnormal mitotic spindles in many human tumors. In human cells, overexpression of the cyclin-dependent kinase (Cdk)2 partner cyclin A during a prolonged S phase produces extra centrosomes, called centrosome reduplication. Cdk2 activity protects the Mps1 protein kinase from proteasome-mediated degradation, and we demonstrate here that Mps1 mediates cyclin A-dependent centrosome reduplication. Overexpression of cyclin A or a brief proteasome inhibition increases the centrosomal levels of Mps1, whereas depletion of Cdk2 leads to the proteasome-dependent loss of Mps1 from centrosomes only. When a Cdk2 phosphorylation site within Mps1 (T468) is mutated to alanine, Mps1 cannot accumulate at centrosomes or participate in centrosome duplication. In contrast, phosphomimetic mutations at T468 or deletion of the region surrounding T468 prevent the proteasome-dependent removal of Mps1 from centrosomes in the absence of Cdk2 activity. Moreover, cyclin A-dependent centrosome reduplication requires Mps1, and these stabilizing Mps1 mutations cause centrosome reduplication, bypassing cyclin A. Together, our data demonstrate that the region surrounding T468 contains a motif that regulates the accumulation of Mps1 at centrosomes. We suggest that phosphorylation of T468 attenuates the degradation of Mps1 at centrosomes and that preventing this degradation is necessary and sufficient to cause centrosome reduplication in human cells.


2010 ◽  
Vol 190 (2) ◽  
pp. 209-222 ◽  
Author(s):  
Romilde Manzoni ◽  
Francesca Montani ◽  
Clara Visintin ◽  
Fabrice Caudron ◽  
Andrea Ciliberto ◽  
...  

In budding yeast, the phosphatase Cdc14 orchestrates progress through anaphase and mitotic exit, thereby resetting the cell cycle for a new round of cell division. Two consecutive pathways, Cdc fourteen early anaphase release (FEAR) and mitotic exit network (MEN), contribute to the progressive activation of Cdc14 by regulating its release from the nucleolus, where it is kept inactive by Cfi1. In this study, we show that Cdc14 activation requires the polo-like kinase Cdc5 together with either Clb–cyclin-dependent kinase (Cdk) or the MEN kinase Dbf2. Once active, Cdc14 triggers a negative feedback loop that, in the presence of stable levels of mitotic cyclins, generates periodic cycles of Cdc14 release and sequestration. Similar phenotypes have been described for yeast bud formation and centrosome duplication. A common theme emerges where events that must happen only once per cycle, although intrinsically capable of oscillations, are limited to one occurrence by the cyclin–Cdk cell cycle engine.


1999 ◽  
Vol 96 (6) ◽  
pp. 2817-2822 ◽  
Author(s):  
K. R. Lacey ◽  
P. K. Jackson ◽  
T. Stearns

2005 ◽  
Vol 25 (1_suppl) ◽  
pp. S309-S309
Author(s):  
Svetlana Pundik ◽  
W David Lust ◽  
Jose Valerio ◽  
Michael Buczek ◽  
Randall D York ◽  
...  

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