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Relaxation Oscillators
Published in James E. Ferrell, Systems Biology of Cell Signaling, 2021
The current view of regulatory circuit that drives the cell cycle is shown schematically in Figure 15.4. Oscillations are now know to be driven by the synthesis of several related mitotic cyclin proteins (cyclins B1α, B1β, B2, B4, B5, and A1, here collectively referred to as cyclin B). The cyclin B binds with high affinity to Cdk1, which is present in modest excess, and when the cyclin B–Cdk1 complex is in the right phosphorylation state, it is active as a protein kinase, phosphorylating hundreds of substrate proteins at many hundreds of phosphorylation sites. The collective effect of these phosphorylations is the dramatic cellular changes of mitotic entry, including chromatin condensation, nuclear envelope breakdown, vesiculation of the golgi, endoplasmic reticulum, and mitochondria, and reorganization of the microtubules into a football-shaped spindle.
Carnosic acid exhibits antiproliferative and proapoptotic effects in tumoral NCI-H460 and nontumoral IMR-90 lung cells
Published in Journal of Toxicology and Environmental Health, Part A, 2020
Amanda Cristina Corveloni, Simone Cristine Semprebon, Adrivanio Baranoski, Bruna Isabela Biazi, Thalita Alves Zanetti, Mário Sérgio Mantovani
Cyclin-dependent kinases (CDKs) drive cell cycle progression, and changes in CDK activities are regulated by cyclins D, E, A, and B, ensuring that kinase activity is regulated in a time-specific manner (Malumbres and Barbacid 2009). In the present study, IMR-90 cells exposed to CA exhibited a decrease in mRNA levels of CCNA2, a gene that encodes cyclin A2, as well as CCNB1 and CCNB2 that encode cyclin B. Cyclins A2, B1, and B2 are essential for cell cycle progression. Cyclin A/CDK2 is important in the control of DNA replication (Yam, Fung, and Poon 2002), and together with cyclin E/CDK2, acts by limiting replication to only once per cycle (Woo and Poon 2003). Cyclin A2 also activates CDK1 at the end of the G2 phase to initiate mitosis (Malumbres and Barbacid 2009). Progression from G2 phase to M phase is driven by the activation of cyclin B/CDK1. This complex is able to promote several cellular reorganizations that occur at the beginning of mitosis, such as mitotic spindle assembly, condensation of chromosomes, nuclear envelope rupture, and cytoskeletal reorganization (Gavet and Pines 2010). Downregulation of CCNA2, CCNB1, and CCNB2 by CA may be related to cell cycle arrest at the G0/G1 and G2/M phases in IMR-90 cells. In NCI-H460 cells, no marked alterations were observed in cyclin expression, as it may be more resistant to CA treatment. Previous investigators reported that CA cell cycle arrest may be attributed to the downregulation of cyclins A2 and B, and via modulation of other cell cycle components (Cortese et al. 2016; Visanji, Thompson, and Padfield 2006). Cortese et al. (2016) demonstrated that CA initiated G2 phase arrest mediated by downregulation of cyclin B1, diminished CDK activity, and enhanced p21 levels in human glioblastoma cells. CA treatment of Caco-2 cells led to a gradual accumulation of cells prior to prometaphase that was associated with a decrease in cyclin A levels (Visanji, Thompson, and Padfield 2006).