China
Africa
Explore chapters and articles related to this topic
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 hypophosphorylated form of Rb binds to and inhibits the activity of the transcriptional factor E2F.175–179 Phosphorylation of Rb by cyclin D-Cdk4 reduces its ability to form inhibitory complexes with E2F.173 In cells lacking functional Rb, the microinjection of antibodies or antisense plasmids to cyclin Dl does not prevent entry into S phase,154,180,181 whereas the microinjection of cyclin E antibody prevents cell cycle progression.154 These observations further support the contention that cyclin E plays a role in the signalling of cell cycle progression downstream of the point at which cyclin D has its regulatory effect.
Future perspectives in peritoneal malignancy
Published in Tom Cecil, John Bunni, Akash Mehta, A Practical Guide to Peritoneal Malignancy, 2019
Ioanna Panagiotopoulou, Alexios Tzivanakis, Tom Cecil
The most frequently mutated tumour suppressor genes detected in malignant mesothelioma are the cyclin-dependent kinase inhibitor 2A/alternative reading frame (CDKN2A/ARF), neurofibromatosis type 2 (NF2) and BRCA-1 associated protein-1 (BAP-1) [49]. CDKN2A encodes p16INK4a that controls the cell cycle via the cyclin-dependent kinase 4/cyclin D-retinoblastoma protein pathway [49,53, 54]. The ARF gene encodes p14ARF that, in turn, regulates p53. Therefore, a deletion of CDKN2A and ARF results in the inactivation of two tumour suppressor pathways [49]. The NF2 gene encodes a tumour suppressor protein named merlin that mediates inhibition of cell proliferation via the mTOR pathway. Therefore, NF2 loss of function in mesothelioma results in upregulated mTOR activity and increased cell proliferation [49,55]. BAP1 encodes a nuclear ubiquitin C-terminal hydrolase that is an enzyme involved in numerous processes such as cell proliferation, DNA repair and transcription regulation [49,55]. BAP1 enhances the BRCA-1 mediated inhibition of cell proliferation by acting on the host cell factor-1 transcriptional scaffolding subunit [49].
CDK Inhibitors in Leukemia and Lymphoma
Published in Gertjan J. L. Kaspers, Bertrand Coiffier, Michael C. Heinrich, Elihu Estey, Innovative Leukemia and Lymphoma Therapy, 2019
Cyclin D1 is a multifunctional protein that plays a critical role not only as a partner of CDK4/6 (see above) in the regulation of the cell cycle (e.g., the G1/S transition) but also as a transcriptional regulator by modulating the activity of several transcriptional factors (e.g., STAT3) that are CDK-independent. This may explain why cyclin D1 is not only involved in cell cycle progression but also in cell growth and survival (25). Cyclin D1 binds to transcriptional factors STAT3 and NeuroD and inhibits their transcriptional activity, which may be related to the modulation of cell differentiation. Cyclin D1 also interacts with histone deacetylases and, in so doing, blocks access of transcriptional factors to the promoter and inhibits loading of initiation complex (26). Cyclin D1, as an oncogene, also plays an important role in carcinogenesis, probably by driving cells into the S phase and cooperating with various oncogenes (such as Myc and Ras) in malignant transformation. Rearrangement of the cyclin D1 locus and/or overexpression of cyclin D1 have been reported in many human tumors, particularly mantle cell lymphoma (27).
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
Cyclin D1 promotes progression through the G1 phase of the cell cycle. Over expression of cyclin D1 has been reported in various tumours like oesophageal carcinoma, hepatocellular carcinoma, lung carcinoma, and head and neck carcinoma. It is reported that cyclin D1 protein expression is significantly altered from epithelial dysplasia to oral squamous cell carcinomas [23]. CDK4 is one of the main players in cell cycle. Progression from G1 phase to S phase of the mammalian cell cycle is controlled by Cyclin D1 in conjunction with their catalytic partners CDK4 [24]. Cyclin D1/CDK4 complexes form in cytoplasm and are then translocated to the nucleus to promote G1/S transition and are responsible for inactivation of Rb proteins [25]. We predicted whether circYap could bind to Cyclin D1 or CDK4 by RPIseq. The scores indicate circYap may interact with Cyclin D1 and CDK4, respectively. We hypothesized that circYap may bind CDK4 and Cyclin D1 to influence the cell cycle. Next, we used RIP and RNA pull-down assays to confirm the above conjecture. We found that circYap could only bind to CDK4, but could not bind to Cyclin D1. Further experiments showed that overexpression of circYap significantly reduced the interaction between CDK4 and Cyclin D1. Therefore, we demonstrated that circYap may bind CDK4, thereby inhibiting the formation of Cyclin D1 and CDK4 complex, resulting in the retention of Cyclin D1 in the cytoplasm, and leading to cell cycle arrest. Thus, we clarify the mechanism that Cyclin D1 involves in OSCC from another aspect.
The Effects of Quercetin on the Apoptosis of Human Breast Cancer Cell Lines MCF-7 and MDA-MB-231: A Systematic Review
Published in Nutrition and Cancer, 2022
Roghayeh Molani Gol, Sorayya Kheirouri
QT reduces levels of Twist and it in turn leads to inhibition of cell proliferation and induction of apoptosis through blocking of cell cycle by down-regulation of cyclin D1. Then, it results to accumulation of cells at the G1 phase which further facilitates G1/S checkpoint arrest (77). Binding of cyclin D1 to CDKs is vital for cell cycle progression toward the S phase and later to initiate cell division. The function of CDKs strongly regulated by few cell-cycle inhibitors such as p16, p21, and p27 proteins. These proteins inhibit cyclin-CDK complexes catalytic activity and causing cell-cycle arrest (126). Foubert et al. reported that in QT treated MCF-7 cells, QT leads to down-regulation of Twist and it in turn causes overexpression of p16 and p21 (126). Ansieau et al. showed that Twist represses p21 and p16 transcription (127). Previous studies reported that p21 may play a critical role in the induction of apoptosis in response to QT (83, 128).
Pterostilbene as a Phytochemical Compound Induces Signaling Pathways Involved in the Apoptosis and Death of Mutant P53-Breast Cancer Cell Lines
Published in Nutrition and Cancer, 2021
Asmaa M. Elsherbini, Salah A. Sheweita, Ahmed S. Sultan
Cyclin D1 plays a critical role in oncogenic transformation, neoplastic growth, metastases, and resistance to apoptosis caused by chemotherapeutic agents (50). Tamoxifen resistance in ER + breast cancer has been shown to be associated with overexpression of Cyclin D1 protein in ErbB2-positive breast cancer (51). Several studies have shown that the upregulation of AKT/mTOR/eIF4E and β-catenin signaling pathways triggered the protein expression of Cyclin D1 leading to cell growth and apoptotic rescue (52, 53). Supporting our finding, upon PT treatment, β-catenin, along with its upstream regulator GSK3β and its downstream target c-myc were significantly regulated in breast cancer cells and also suppressed colon tumorgenesis in rats (54). Moreover, PT treatment regulated the protein expression of Cyclin D1 in TNBC and ER + breast cancer cells, and also in the xenograft mouse model (48).