scholarly journals Arresting developments in the cardiac myocyte cell cycle: Role of cyclin-dependent kinase inhibitors

1998 ◽  
Vol 39 (2) ◽  
pp. 301-311 ◽  
Author(s):  
G Brooks
Keyword(s):  
Cell Cycle ◽  
Cardiac Myocyte ◽  
Kinase Inhibitors ◽  
Cyclin Dependent Kinase

scholarly journals Role of the Combination of Cyclin-Dependent Kinase Inhibitors (CDKI) and Radiotherapy (RT) in the Treatment of Metastatic Breast Cancer (MBC): Advantages and Risks in Clinical Practice

2021 ◽  
Vol 11 ◽  
Author(s):  
Ambrogio Gagliano ◽  
Angela Prestifilippo ◽  
Ornella Cantale ◽  
Gianluca Ferini ◽  
Giacomo Fisichella ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Cycle ◽  
Metastatic Breast Cancer ◽  
Gold Standard ◽  
Kinase Inhibitors ◽  
Metastatic Breast ◽  
Cyclin Dependent Kinase ◽  
Safety And Efficacy ◽  
Definite Evidence

Targeting cell cycle has become the gold standard for metastatic breast cancer (MBC), being cyclin-dependent kinase inhibitors (CDKIs) cornerstones of its treatment, alongside radiotherapy (RT). To date, no definite evidence regarding safety and efficacy of the combination of CDKIs plus radiotherapy (RT) is currently available. Purpose of this review is to collect data in favor or against the feasibility of the association of CDKIs + RT, describing its potential adverse events. Our review shows how CDKI + RT allows an overall satisfying disease control, proving to be effective and causing a grade of toxicity mainly influenced by the site of irradiation, leaning to favourable outcomes for sites as liver, spine or brain and to poorer outcomes for thoracic lesions or sites close to viscera; controversial evidence is instead for bone treatment. Toxicity also varies from patient to patient. To sum up, our contribution enriches and enlightens a still indefinite field regarding the feasibility of CDKIs + RT, giving cues for innovative clinical management of hormone-responsive MBC.

Survival and Cell Cycle Control in Early Hematopoiesis: Role of Bcl-2, and the Cyclin Dependent Kinase Inhibitors P27 and P21

2002 ◽  
Vol 43 (1) ◽  
pp. 51-57 ◽  
Author(s):  
Maria Marone ◽  
Giuseppina Bonanno ◽  
Sergio Rutella ◽  
Giuseppe Leone ◽  
Giovanni Scambia ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Kinase Inhibitors ◽  
Cell Cycle Control ◽  
Cyclin Dependent Kinase

scholarly journals The Role of Cdh1p in Maintaining Genomic Stability in Budding Yeast

Genetics ◽  
2003 ◽  
Vol 165 (2) ◽  
pp. 489-503 ◽  
Author(s):  
Karen E Ross ◽  
Orna Cohen-Fix
Keyword(s):  
Cell Cycle ◽  
Chromosome Segregation ◽  
Spindle Assembly Checkpoint ◽  
Chromosome Loss ◽  
Cyclin Dependent Kinase ◽  
Anaphase Promoting Complex ◽  
Growth Defects ◽  
Genes Encoding ◽  
Specificity Factor

Abstract Cdh1p, a substrate specificity factor for the cell cycle-regulated ubiquitin ligase, the anaphase-promoting complex/cyclosome (APC/C), promotes exit from mitosis by directing the degradation of a number of proteins, including the mitotic cyclins. Here we present evidence that Cdh1p activity at the M/G1 transition is important not only for mitotic exit but also for high-fidelity chromosome segregation in the subsequent cell cycle. CDH1 showed genetic interactions with MAD2 and PDS1, genes encoding components of the mitotic spindle assembly checkpoint that acts at metaphase to prevent premature chromosome segregation. Unlike cdh1Δ and mad2Δ single mutants, the mad2Δ cdh1Δ double mutant grew slowly and exhibited high rates of chromosome and plasmid loss. Simultaneous deletion of PDS1 and CDH1 caused extensive chromosome missegregation and cell death. Our data suggest that at least part of the chromosome loss can be attributed to kinetochore/spindle problems. Our data further suggest that Cdh1p and Sic1p, a Cdc28p/Clb inhibitor, have overlapping as well as nonoverlapping roles in ensuring proper chromosome segregation. The severe growth defects of both mad2Δ cdh1Δ and pds1Δ cdh1Δ strains were rescued by overexpressing Swe1p, a G2/M inhibitor of the cyclin-dependent kinase, Cdc28p/Clb. We propose that the failure to degrade cyclins at the end of mitosis leaves cdh1Δ mutant strains with abnormal Cdc28p/Clb activity that interferes with proper chromosome segregation.

Synthesis and anticancer activity of some pyrido[2,3-d]pyrimidine derivatives as apoptosis inducers and cyclin-dependent kinase inhibitors

2019 ◽  
Vol 11 (18) ◽  
pp. 2395-2414 ◽  
Author(s):  
Safinaz E-S Abbas ◽  
Riham F George ◽  
Eman M Samir ◽  
Mostafa MA Aref ◽  
Hatem A Abdel-Aziz
Keyword(s):  
Cell Cycle ◽  
Anticancer Agents ◽  
Kinase Inhibitors ◽  
Cytotoxic Agents ◽  
Cyclin Dependent Kinase ◽  
Apoptosis Induction ◽  
Pyrimidine Derivatives ◽  
Induced Apoptosis ◽  
Emergence Of Resistance ◽  
Mcf 7

Aim: Due to emergence of resistance to available anticancer agents, there is a need to search for new cytotoxic agents. Methods: Pyrido[2,3- d]pyrimidines (4–6) and their tricyclic derivatives (7–13) were prepared and screened for their cytotoxicity against breast MCF-7, prostate PC-3 and lung A-549 cancer cell lines as well as normal fibroblasts WI-38. Results: The most active compounds were 6b, 6e and 8d compared with doxorubicin. Moreover, compounds 6b and 8d induced apoptosis in PC-3 and MCF-7, respectively via activation of CASP3 (in PC-3 only), Bax, p53 and down regulation of Bcl2 in addition to CDK4/6 inhibition. Conclusion: Pyrido[2,3- d]pyrimidine represents an important core for discovery of new potent cytotoxic agents acting on the cell cycle via apoptosis induction through either intrinsic or extrinsic pathways.

scholarly journals Expression and modulation of p42/p44 MAPKs and cell cycle regulatory proteins in rat pancreas regeneration

1999 ◽  
Vol 277 (5) ◽  
pp. G953-G959 ◽  
Author(s):  
Jean Morisset ◽  
JoséCristobal Aliaga ◽  
Ezéquiel L. Calvo ◽  
Judith Bourassa ◽  
Nathalie Rivard
Keyword(s):  
Cell Cycle ◽  
Molecular Mechanisms ◽  
Kinase Inhibitors ◽  
Regulatory Proteins ◽  
Mitogen Activated Protein Kinase ◽  
Cyclin Dependent Kinase ◽  
Mapk Activation ◽  
Pancreas Regeneration ◽  
Mitogen Activated Protein ◽  
Cell Cycle Regulatory Proteins

Pancreatic growth occurs after CCK, CCK-induced pancreatitis, and pancreatectomy; the mechanisms involved remain unknown. This study evaluates mitogen-activated protein kinase (MAPK) activation and expression of cell cycle regulatory proteins after pancreatectomy to understand the cellular and molecular mechanisms involved in pancreas regeneration. Rats were killed 1–12 days after pancreatectomy, and p42/p44 MAPK activation, expression of the cyclins D and E, cyclin-dependent kinase (Cdk)-2 activity, retinoblastoma protein (pRb) hyperphosphorylation, and expression of the cyclin kinase inhibitors p15, p21, and p27 were examined. Pancreatic remnants exhibited sustained p42/p44 MAPK activation within 8 h. Cyclins D1 and E showed maximal expression after 2 and 6 days, coinciding with maximal hyperphosphorylation of pRb and Cdk2 activity. The expression of p15 vanished after 12 h, p27 disappeared gradually, and p21 increased early. The p27 complexed with Cdk2 dissociated after 2 days, whereas p21 associated in a reverse fashion. In conclusion, sustained activation of p42/p44 MAPKs and Cdk2 along with overexpression of cyclins D1 and E and reduction of p15 and p27 cyclin inhibitors occurred early after pancreatectomy and are active factors involved in signaling that leads to pancreas regeneration.

scholarly journals Review of rationale and progress toward targeting cyclin-dependent kinase 2 (CDK2) for male contraception†

2020 ◽  
Vol 103 (2) ◽  
pp. 357-367
Author(s):  
Erik B Faber ◽  
Nan Wang ◽  
Gunda I Georg
Keyword(s):  
Cell Cycle ◽  
Binding Site ◽  
Knockout Mice ◽  
Male Contraception ◽  
Cyclin Dependent Kinase ◽  
Compensatory Mechanisms ◽  
Binding Partner ◽  
Male Contraceptive ◽  
Clinical Stages

Abstract Cyclin-dependent kinase 2 (CDK2) is a member of the larger cell cycle regulating CDK family of kinases, activated by binding partner cyclins as its name suggests. Despite its canonical role in mitosis, CDK2 knockout mice are viable but sterile, suggesting compensatory mechanisms for loss of CDK2 in mitosis but not meiosis. Here, we review the literature surrounding the role of CDK2 in meiosis, particularly a cyclin-independent role in complex with another activator, Speedy 1 (SPY1). From this evidence, we suggest that CDK2 could be a viable nonhormonal male contraceptive target. Finally, we review the literature of pertinent CDK2 inhibitors from the preclinical to clinical stages, mostly developed to treat various cancers. To date, there is no potent yet selective CDK2 inhibitor that could be repurposed as a contraceptive without appreciable off-target toxicity. To achieve selectivity for CDK2 over closely related kinases, developing compounds that bind outside the conserved adenosine triphosphate-binding site may be necessary.

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