Growth Suppression and Mitotic Defect Induced by JNJ-7706621, an Inhibitor of Cyclin-Dependent Kinases and Aurora Kinases

2012 ◽  
Vol 12 (6) ◽  
pp. 625-639 ◽  
Author(s):  
A. Matsuhashi ◽  
T. Ohno ◽  
M. Kimura ◽  
A. Hara ◽  
M. Saio ◽  
...  
1996 ◽  
Vol 271 (31) ◽  
pp. 18961-18965 ◽  
Author(s):  
Antonio De Luca ◽  
Manoranjan Santra ◽  
Alfonso Baldi ◽  
Antonio Giordano ◽  
Renato V. Iozzo

2005 ◽  
Vol 65 (19) ◽  
pp. 9038-9046 ◽  
Author(s):  
Stuart Emanuel ◽  
Catherine A. Rugg ◽  
Robert H. Gruninger ◽  
Ronghui Lin ◽  
Angel Fuentes-Pesquera ◽  
...  

2021 ◽  
Vol 22 (4) ◽  
pp. 1936
Author(s):  
Hyo Jin Kim ◽  
Jongchan Kim

Aurora kinases are serine/threonine kinases required for cell proliferation and are overexpressed in many human cancers. Targeting Aurora kinases has been a therapeutic strategy in cancer treatment. Here, we attempted to identify a deubiquitinase (DUB) that regulates Aurora kinase A (Aurora-A) protein stability and/or kinase activity as a potential cancer therapeutic target. Through pull-down assays with the human DUB library, we identified OTUD6A as an Aurora-A-specific DUB. OTUD6A interacts with Aurora-A through OTU and kinase domains, respectively, and deubiquitinates Aurora-A. Notably, OTUD6A promotes the protein half-life of Aurora-A and activates Aurora-A by increasing phosphorylation at threonine 288 of Aurora-A. From qPCR screening, we identified and validated that the cancer gene CKS2 encoding Cyclin-dependent kinases regulatory subunit 2 is the most upregulated cell cycle regulator when OTUD6A is overexpressed. The results suggest that OTUD6A may serve as a therapeutic target in human cancers.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Esmee Koedoot ◽  
Liesanne Wolters ◽  
Marcel Smid ◽  
Peter Stoilov ◽  
Gerhard A. Burger ◽  
...  

AbstractScreening for effective candidate drugs for breast cancer has shifted from two-dimensional (2D) to three-dimensional (3D) cultures. Here we systematically compared the transcriptomes of these different culture conditions by RNAseq of 14 BC cell lines cultured in both 2D and 3D conditions. All 3D BC cell cultures demonstrated increased mitochondrial metabolism and downregulated cell cycle programs. Luminal BC cells in 3D demonstrated overall limited reprogramming. 3D basal B BC cells showed increased expression of extracellular matrix (ECM) interaction genes, which coincides with an invasive phenotype not observed in other BC cells. Genes downregulated in 3D were associated with metastatic disease progression in BC patients, including cyclin dependent kinases and aurora kinases. Furthermore, the overall correlation of the cell line transcriptome to the BC patient transcriptome was increased in 3D cultures for all TNBC cell lines. To define the most optimal culture conditions to study the oncogenic pathway of interest, an open source bioinformatics strategy was established.


2011 ◽  
Vol 435 (1) ◽  
pp. 17-31 ◽  
Author(s):  
Hoi Tang Ma ◽  
Randy Y. C. Poon

Mitosis is associated with profound changes in cell physiology and a spectacular surge in protein phosphorylation. To accomplish these, a remarkably large portion of the kinome is involved in the process. In the present review, we will focus on classic mitotic kinases, such as cyclin-dependent kinases, Polo-like kinases and Aurora kinases, as well as more recently characterized players such as NIMA (never in mitosis in Aspergillus nidulans)-related kinases, Greatwall and Haspin. Together, these kinases co-ordinate the proper timing and fidelity of processes including centrosomal functions, spindle assembly and microtubule–kinetochore attachment, as well as sister chromatid separation and cytokinesis. A recurrent theme of the mitotic kinase network is the prevalence of elaborated feedback loops that ensure bistable conditions. Sequential phosphorylation and priming phosphorylation on substrates are also frequently employed. Another important concept is the role of scaffolds, such as centrosomes for protein kinases during mitosis. Elucidating the entire repertoire of mitotic kinases, their functions, regulation and interactions is critical for our understanding of normal cell growth and in diseases such as cancers.


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