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Naturally Occurring Histone Deacetylase (HDAC) Inhibitors in the Treatment of Cancers
Published in Namrita Lall, Medicinal Plants for Cosmetics, Health and Diseases, 2022
Sujatha Puttalingaiah, Murthy V. Greeshma, Mahadevaswamy G. Kuruburu, Venugopal R. Bovilla, SubbaRao V. Madhunapantula
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.
Immunotherapy in Head and Neck Cancers
Published in R James A England, Eamon Shamil, Rajeev Mathew, Manohar Bance, Pavol Surda, Jemy Jose, Omar Hilmi, Adam J Donne, Scott-Brown's Essential Otorhinolaryngology, 2022
The Wee1 kinase regulates entry into mitosis, by negatively controlling CDK1 and Chk2. AZD-1775 is an agent shown to potentiate DNA-damaging agents in vitro and in vivo, and it is currently undergoing phase I trials.
Antitubulin Agents
Published in David E. Thurston, Ilona Pysz, 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.
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.
Cell cycle dysregulation on prenatal and postnatal arsenic exposure in skin of Wistar rat neonates
Published in Xenobiotica, 2023
Navneet Kumar, Astha Mathur, Suresh Kumar Bunker, Placheril J. John
There was a dose dependent decrease in transcript levels of cyclin A and cyclin B1 with increasing dose groups, whereas a similar increase in transcript levels of cyclin E1 with increasing dose groups. We also observed the downregulation of transcript levels of both CDK1 and CDK2 in a dose dependent manner. The increased expression of cyclin E1 has been shown to be involved in accelerated G1 to S phase transition (Resnitzky et al. 1994). The observed increase in cyclin E1 transcript expression levels can be a sign of increasing amount of cells transitioning to S phase. The cyclin A/CDK2 complex causes the transition of the cell cycle from the S phase to the G2 phase, and cyclin A then activates CDK1 to cause the cell to enter the M phase. The cyclin B/CDK1 complex maintains CDK1 activity during mitosis (Kalous et al. 2020). Disruption in the levels of CDK/cyclin complexes can result in cell cycle arrest in S phase and G2/M phase.
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.