Antitubulin Agents
David E. Thurston, Ilona Pysz in Chemistry and Pharmacology of Anticancer Drugs, 2021
The Polo-Like Kinases (PLKs) are a family of conserved serine/threonine kinases that are important regulators of the cell cycle through G2 and some phases of mitosis, including mitotic entry and exit, and cytokinesis. The “Polo” domain is named after the original protein encoded by the Polo gene of Drosophila melanogaster. These proteins are involved in the formation of, and modifications to, the mitotic spindle, and in the activation of CDK/Cyclin complexes during the M phase of the cell cycle. The PLKs are characterized by an amino terminal catalytic domain, and a carboxy terminal noncatalytic domain consisting of three blocks of conserved sequences known as Polo boxes which form one single functional domain. Mammalian PLKs include PLK1 (also known as STPK13), PLK2 (also known as SNK), PLK3 (also known as CNK, FNK, and PRK), PLK4 (also known as SAK or STK18), and PLK5. In particular, PLK1 acts in concert with Cyclin-dependent kinase 1 (Cyclin B1) and the Aurora kinases to orchestrate a wide range of critical cell-cycle events.
Naturally Occurring Histone Deacetylase (HDAC) Inhibitors in the Treatment of Cancers
Namrita Lall in Medicinal Plants for Cosmetics, Health and Diseases, 2022
Class III HDACs, which contain SIRT1, are known phosphoproteins. The cell cycle–dependent kinase cyclin B/Cdk1 phosphorylates SIRT1 (Beausoleil et al., 2004). AMPK has been shown to increase intracellular NAD+ levels, which in turn enhances SIRT1 deacetylation activity (Canto et al., 2009). Activation of the cAMP signaling pathway induces rapid deacetylation of SIRT1 substrates, which is independent of changes in NAD+ levels (Gerhart-Hines et al., 2011). Activation of the cAMP signaling pathway induces rapid deacetylation of SIRT1 substrates independent of changes in NAD+ levels (Gerhart-Hines et al., 2011). HDAC activities can be modulated by the protein–protein interaction and the post-translational modification by the phosphorylation of different complexes associated with the HDAC.
Garlic
Robert E.C. Wildman, Richard S. Bruno in Handbook of Nutraceuticals and Functional Foods, 2019
Evidence indicates that garlic constituents (i.e., DADS, DATS, S-allylmercaptocysteine [SAMC], ajoene) have the ability to suppress proliferation of several different cancer cells by blocking cell-cycle progression and/or causing apoptosis (also known as programmed cell death).134–136 Several mechanisms have been cited for the effect of garlic constituents on cell cycle arrest, including reduced Cdk1/cyclin B kinase activity, activation of extracellular signal-regulated kinases (ERK1/2), or induction of phosphorylated checkpoint kinase-1.134,137,138 Knowles and Milner139 showed that the DADS-mediated suppression of Cdk1 kinase activity during cell-cycle arrest in G2/M was not due to direct interaction with the protein, but was associated with (a) a temporal and dose-dependent increase in cyclin B1 protein level, (b) a reduction in the level of Cdk1–cyclin B1 complex formation, (c) inactivating hyperphosphorylation of Cdk1, and (d) a decrease in Cdc25C protein level. The evidence suggests a complex and coordinated interaction of many factors for the observed DADS-induced cell-cycle arrest. Furthermore, gene expression analysis suggested that alterations in DNA repair and cellular adhesion factors may also be involved in the G2/M block following DADS exposure.140
Histomorphological changes and molecular mechanisms underlying the ameliorative effect of resveratrol on the liver of silver nanoparticles-exposed rats
Published in Ultrastructural Pathology, 2022
Shaimaa A. Abdelrahman, Abeer A. Mahmoud, Abeer A. Abdelrahman, Walaa Samy, Ebtehal Zaid Hassen Saleh
RSV supplementation also had a role in upregulation of mRNA expression of ADORA3 (adenosine A3 receptor) that was significantly downregulated with exposure to AgNPs. ADORA3 is one of the G-protein-coupled receptors involved in intracellular signaling pathways and have a protective role in inflammation-related diseases and downregulation of ADORA3, is associated with tissue damage.69,70 On the contrary, PAI-1 expression level (also known as plasminogen activator inhibitor-1), was upregulated in AgNPs group. It has been reported as a biomarker for diagnosis of inflammation.42 Cyclin-dependent kinase 1 (also known as CDK1) is another protein that functions as a serine/threonine kinase and is a key player in cell cycle regulation.71 It showed significant upregulation in AgNPs group that was reversed by the effect of RSV.
Identification and validation of core genes in tumor-educated platelets for human gastrointestinal tumor diagnosis using network-based transcriptomic analysis
Published in Platelets, 2023
Yuhong Jiang, Jun He, Xiaobo Wang, Chao Liu, Weihan Zhou, Dekun Liu, Zhushu Guo, Kuijie Liu
Next, the association between the proteins encoded by these TEP DEGs was investigated using PPI network analysis. We find that among the TEP DEGs of the core subnetwork, CDK1 and HSPA5 have the highest degree values. Thereby, this two-gene diagnostic signature may be used for GI cancer detection. Cyclin-dependent kinase (CDK1), also known as cell division control protein 2 (CDC2), is essential for directing the cell cycle in all cell types.47 Heat Shock Protein Family A (Hsp70) Member 5 (HSPA5), also named Glucose-Regulated Protein 78 (GRP78) or immunoglobulin heavy chain binding protein (BiP), is a chaperone heat shock protein that expresses in all eukaryotes on the membrane of Endoplasmic Reticulum (ER).48 GRP78 is overexpressed on the membranes of many cancer cells, which makes GI malignancies like PAAD and CRC more aggressive.49 Although according to previous studies,50 HSPA5 is aberrantly activated in tumor tissues compared to normal control, however, its expression changes in TEPs seems to be the opposite as revealed by our study. Therefore, here we discover a novel two-gene signature specifically in platelets for GI tumor diagnosis.
Genistein Suppresses v-Src-Driven Proliferative Activity by Arresting the Cell-Cycle at G2/M through Increasing p21 Level in Src-Activated Human Gallbladder Carcinoma cells
Published in Nutrition and Cancer, 2021
Misaki Ono, Mikako Takeshima, Asuka Nishi, Takako Higuchi, Shuji Nakano
Because genistein was shown to inhibit v-Src-driven cellular growth through G2/M cell cycle arrest, we examined the effects of genistein on cell cycle related proteins in HAG/src3-1 cells. Upon treatment with genistein, the protein levels of p53 and p21 were significantly increased when compared with those of untreated control, while phosphorylated p21 was significantly decreased. On the other hand, the expression levels of p53, p21, and phosphorylated p21 were not affected by the treatment of either daidzein, glycitein, or equol. It has been shown that expression of cyclins and CDK1 proteins play a critical role in the G2/M transition of the cell cycle. Activation of CDK1 is controlled at several steps including cyclin binding and phosphorylation of CDK1 at Thr161 (23). However, the critical regulatory step in activating CDK1 during progression into mitosis appears to be dephosphorylation of CDK1 at Tyr15 and Thr14 (24). Therefore, we examined the expression of major cyclins and CDK1/2 as well as phosphorylation status of CDK1 at different sites of threonine and tyrosine residues after treatment of isoflavone components. As shown in Figure 3, the expression levels of cyclin A, B1, D, E1, CDK2, and CDK1 as well as the levels of phosphorylated CDK1 at Thr14, Tyr15, and Thr161 were not affected by any of those isoflavones.
Related Knowledge Centers
- Cyclin
- Protein
- Saccharomyces Cerevisiae
- Phosphorylation
- Cell Cycle
- Serine/Threonine-Specific Protein Kinase
- Schizosaccharomyces Pombe
- Gene
- Adenosine Triphosphate
- Hydroxy Group