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Regulation of Airway Smooth Muscle Proliferation by β2-Adrenoceptor Agonists
Published in Alastair G. Stewart, AIRWAY WALL REMODELLING in ASTHMA, 2020
Alastair G. Stewart, Paul R. Tomlinson, Leslie Schachte
The cyclins are a family of proteins which are synthesised at different rates according to the stage in the cell cycle. The key G1 cyclins are cyclins D and E.151 Cyclin D1 was first identified as a product expressed in G1 by mouse macrophage cell line (BAC1.2F5A).152 Cyclins D2 and D3 were identified by using cyclin D1 cDNA as a probe to screen cDNA libraries.152,153 After mitogenic stimulation, cyclin D1 expression is apparent during the G0/G1 transition and reaches maximal levels prior to G1/S transition.152 The oscillation of the levels of expression of cyclin D during the cell cycle is moderate in comparison with other cyclins,151 but its elevation late in G1 is compatible with a role in the passage of cells through the restriction point. A decrease in cyclin D1 accumulation and/or its extrusion from the nucleus may be a prerequisite for the entry of cells into S phase.154
TGF-β signaling in testicular development, spermatogenesis, and infertility
Published in Rajender Singh, Molecular Signaling in Spermatogenesis and Male Infertility, 2019
Poonam Mehta, Meghali Joshi, Rajender Singh
Further exploration of the molecular mechanism of self-renewal revealed the involvement of other signaling pathways that are driven by GDNF. For example, Src family kinases, which activate P13 K/Akt signaling and ultimately N-myc expression, promote SSC proliferation. GDNF also activates Ras signaling, which further upregulates the transcription of cyclin A and cdk2, which are predominantly expressed during spermatogenesis. Thus, they are crucial for G1/S transition of Gfrα-1 positive spermatogonia (59). Microarray analysis of SSCs under the influence of GDNF helped in the identification of other target molecules such as Fgf2 (fibroblast growth factor receptor 2) and Bcl6b (B cell CLL/lymphoma 6, member B), which amplify the effect of GDNF and play roles in the maintenance of SSCs (60).
Bacteria and Bioactive Peptides
Published in Prakash Srinivasan Timiri Shanmugam, Understanding Cancer Therapies, 2018
Ameer Khusro, Chirom Aarti, Paul Agastian
Bacterial toxins have also been known to treat cancer by altering the cellular processes that maintain proliferation, apoptosis, and differentiation. Cytolethal distending toxins (CDTs) and the cycle-inhibiting factor (Cif) are cell-cycle inhibitors that block mitosis and compromise the immune system by inhibiting clonal expansion of lymphocytes. In contrast, the cytotoxic necrotizing factor (CNF), a cell-cycle stimulator, promotes cellular proliferation and interferes with cell differentiation (Nougayrede et al. 2005). CNF is a cell-cycle stimulator released by E. coli. CNF induces G1-S transition and causes DNA replication. CDTs are present in Campylobacter jejuni and S. typhi, while Cif is found in enteropathogenic (EPEC) and enterohemorrhagic (EHEC) E. coli. The anticancer activity of toxins shows reduced side effects compared to traditional treatments. Further the antitumor activity can be enhanced by combining bacterial toxins with anticancer drugs or irradiation (Carswell et al. 1975).
Effects of MFG-E8 expression on the biological characteristics of ovarian cancer cells via the AKT/mTOR/S6K signalling pathway
Published in Journal of Obstetrics and Gynaecology, 2023
Na Li, Yazhuo Wang, Lin Liu, Pei Wang, Xiaohua Wu
The G1/S phase transition of the cell cycle is controlled by cyclin-dependent protein kinases. The kinase-cyclin complex, which modulates the kinase activity, regulates cell cycle progression by targeted phosphorylation. The activity of these complexes peaks during the G1/S transition of the cell cycle and promotes cell mitosis (Lee et al.2019). Cyclin D mainly regulates the G1/S cell cycle transition, and its expression is closely related to the abnormal proliferation of tumours (Blain 2008). Besides, MFG-E8 could promote the proliferation of human pulmonary artery smooth muscle cells via p-Akt/cyclin D1 pathway (Wang et al.2021). Our present study showed consistent changes in cell proliferation and expression of cyclin D1 and CDK4 after MFG-E8 silence. Previous studies have focussed on the role of MFG-E8 in artery smooth muscle cells (VSMC) (Wang et al.2012, 2021), however, our study confirmed that MFG-E8 is involved in cell cycle regulation, which could help us better understand the mechanism of MFG-E8 in tumours.
A Novel Compound Plumercine from Plumeria alba Exhibits Promising Anti-Leukemic Efficacies against B Cell Acute Lymphoblastic Leukemia
Published in Nutrition and Cancer, 2022
Aaheli Chatterjee, Amrita Pal, Santanu Paul
When the results of the molecular docking were compared against standard drugs of ALL, some of them not only showed similar types of potential to be as a suitable drug but also can turn out to be a better phytotherapeutic agent in the future. Among the three bioactive compounds, 13-O-p-Coumaroyl plumieride shows the best interaction with the receptor proteins but at the same time, the druggability and ADMET properties are not very supportive of the fact, so if it comes to future drug development Plumericine and Isoplumericine will be of better choice. It generally acts with the cyclins and CDK involved in G1/S transition phase, so it can be mentioned that the given bioactive compounds can act as potential drug candidates in future for dysregulations in G1/S phase transition. Hence the bioactive compounds obtained from Plumeria alba can act as suitable therapeutic targets for in-silico drug designing for cancer.
circYap inhibits oral squamous cell carcinoma by arresting cell cycle
Published in Acta Odontologica Scandinavica, 2022
Xiao-Yun Zhang, Huifang Tang, Yanping Liu, Nan Du, Songbo Tian, Yong-Qing Dou
To further study the biological role of circYap in OSCC cells, we treated CAL-27 and SCC-4 cells with either circYap overexpression plasmid or si-circYap, and analysed the effects on cell cycle progression. circYap overexpression plasmid induced a strong and reproducible block of the G1/S transition in CAL-27 cells (Figure 3(A)). While, circYap knockdown promoted the G1/S transition in SCC-4 cells (Figure 3(B)). We also investigated some well-known protein factors regulating G1-S transition and cell proliferation, Retinoblastoma (Rb) and Akt proteins. Hypo-phosphorylated Rb can block to activate S-phase genes and so causing G1-S arrest [15]. In CAL-27 cells of circYap overexpression, a reduction of the total amount of Rb protein was observed (Figure 3(C)), moreover, protein decrease was accompanied by a strong decrease of its phosphorylated form, leading to a ratio between p-Rb and Rb down to approximately 40% compared to control conditions, meanwhile, the phosphorylated Akt (p-Akt), which has a crucial role in sustaining cell proliferation [16], was reduced, p-Akt/total Akt ratio was also decreased (Figure 3(C)). Conversely, the increase in Rb, p-Rb and p-Akt protein levels were observed, accompanied by increase of pRb/Rb and pAkt/Akt ratio upon circYap knockdown in SCC-4 cells (Figure 3(D)). In conclusion, these experiments indicate that circYap arrests cell cycle progression in OSCC cells.