Explore chapters and articles related to this topic
Cell Biology for Bioprocessing
Published in Wei-Shou Hu, Cell Culture Bioprocess Engineering, 2020
An important cell cycle checkpoint occurs during the transition from G1 to S phase. The pivotal players in the G1/S phase transition are the regulatory retinoblastoma protein (Rb) and the Cdk4/6-Cyclin D complex (i.e., G1-Cdk complex) (Figure 2.20). In growth-arrested or quiescent cells, Rb is unphosphorylated and binds to and inhibits its E2F. E2F is a transcription factor that activates the transcription of Cyclin E and other proteins for S phase. When in a Rb bound state, it suppresses their transcription. Upon stimulation of mitogen and other cues, ERK (a pivotal player of the growth regulatory signaling system) activates the G1-Cdk complex (via a transcription factor like c-Myc) to phosphorylate Rb. The phosphorylated Rb dissociates from E2F, leading to the activation of expression of Cyclin E that in turn drives Cdk2 activation and the formation of cyclin E-Cdk2 (G1/S Cdk complex). E2F positive feedback on the phosphorylation of Rb causes hyperphosphorylation of Rb and activation of Cdk2. The S phase cyclin, Cyclin A, begins to accumulate in late G1 phase, but is bound by an inhibitor. The G1-Cdk complex facilitates the removal of the inhibition to enable the accumulation of S-Cdk complexes, marking the entry into S phase.
Therapeutic potential of a 2,2’-bipyridine-based vanadium(IV) complex on HepG2 cells: cytotoxic effects and molecular targeting
Published in Egyptian Journal of Basic and Applied Sciences, 2023
Eman Salah El-Shafey, Eslam Samy Elsherbiny
On the other hand, induction of autophagy upon treatment with vanadium complex caused selective recruitment and degradation of the cell-cycle regulator cyclin D1, which contributed to HCC tumorigenesis [53]. Systematically, during the autophagic machinery, cyclin D1 undergoes ubiquitination, proteasomes and autophagic degradation [54]. Ubiquitination of cyclin D1 is known to be mediated by SQSTM1 system, resulting in its degradation that induces cell cycle arrest and reduction in the growth rate [55]. In the current study, results obtained from cell cycle investigation demonstrated the accumulation of cells in G0/G1 suggesting its arrest in this phase. This could be referred to the apparent downregulation in the protein and gene levels of cyclin E, cyclin D1 and CDK2 [36,56]. Thus, our results revealed the anti-tumor activity of vanadium complex to the interplay between apoptosis, autophagy and the cell cycle regulator cyclin D1 in HepG2 cells.
Anti-cancer effects of biosynthesized zinc oxide nanoparticles using Artemisia scoparia in Huh-7 liver cancer cells
Published in Inorganic and Nano-Metal Chemistry, 2022
Anahita Mohammadi Shivyari, Farzaneh Tafvizi, Hassan Noorbazargan
Cyclin D1 and Cyclin E contribute to cell cycle regulation. Cyclin D1 is the first cyclin to be built which directs the phase G1 progress along with CDKs 4/6. It plays an important role in the transition from the G1 phase to S phase.[77] The expression levels of Cyclin D1 in Huh-7 cancer cells significantly decreased after treatment with ZnO NPs, resulting in cell cycle arrest in cancer cells (Figure 10), which was consistent with the flow cytometry cell cycle results. Based on the cell cycle results, following treatment of Huh-7 cells with ZnO NPs and extract, the cell population in the subG1 phase (apoptosis peak) increased compared to the untreated cells, indicating suppression of cancer cells and induction of apoptosis (Figure 11). The cell cycle regulation and apoptosis are closely related. The results suggested that green-synthesized ZnO NPs and the extract are capable of inducing cell cycle arrest.[78,79]
Exposure to long-term evolution radiofrequency electromagnetic fields decreases neuroblastoma cell proliferation via Akt/mTOR-mediated cellular senescence
Published in Journal of Toxicology and Environmental Health, Part A, 2021
Ju Hwan Kim, Sangbong Jeon, Hyung-Do Choi, Jae-Hun Lee, Jun-Sang Bae, Nam Kim, Hyung-Gun Kim, Kyu-Bong Kim, Hak Rim Kim
Rb is known to play critical roles in cell proliferation by negatively regulating the G1/S transition of the cell cycle (Giacinti and Giordano 2006). Rb blocks the E2F family transcription factors that are involved in cell progression from the G1 to the S phase (Goodrich et al. 1991). Phosphorylation of Rb is activated by the cyclin D/CDK4 complex and maintained by cyclin E/CDK2 (Adams 2001). Exposure to 1760 MHz LTE RF-EMF decreased phosphorylated Rb (pRb at Ser807/811) in SH-SY5Y cells in this study (Figure 6(e)). The decreased cyclin D-CDK4 complex and lower levels of CDK2 might reduce phosphorylation of Rb (Ser807/811). That is, less cyclin-CDK complexes might stimulate Rb phosphorylation, consequently inhibiting the G1/S phase transition and producing a delay in the G1 phase. Previously, Choi et al. (2020) reported phosphorylation of Ser780 residues on Rb in ASCs following RF-EMF exposure. All of these sites of Rb may be phosphorylated by activation of cyclin D-CDK4 or cyclin A/E-CDK2 (Chien et al. 2010; Paternot et al. 2006; Zarkowska and Mittnacht 1997).