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G1/S transition

Nicholas L Syn, Pei Li Lim, Li Ren Kong, Lingzhi Wang, Andrea Li-Ann Wong, Chwee Ming Lim, Thomas Kwok Seng Loh, Gerhard Siemeister, Boon Cher Goh, Wen-Son Hsieh
In addition to their canonical roles in regulating cell cycle transition and transcription, cyclin-dependent kinases (CDKs) have been shown to coordinate DNA damage response pathways, suggesting a rational pairing of CDK inhibitors with genotoxic chemotherapeutic agents in the treatment of human malignancies. Here, we report that roniciclib (BAY1000394), a potent pan-CDK inhibitor, displays promising anti-neoplastic activity as a single agent and potentiates cisplatin lethality in preclinical nasopharyngeal carcinoma (NPC) models...
2018: Signal Transduction and Targeted Therapy
Tanggang Deng, Guobei Yan, Xin Song, Lin Xie, Yu Zhou, Jianglin Li, Xiaoxiao Hu, Zhen Li, Jun Hu, Yibin Zhang, Hui Zhang, Yang Sun, Peifu Feng, Dong Wei, Bin Hu, Jing Liu, Weihong Tan, Mao Ye
p21WAF1/CIP1 is a broad-acting cyclin-dependent kinase inhibitor. Its stability is essential for proper cell-cycle progression and cell fate decision. Ubiquitylation by the multiple E3 ubiquitin ligase complexes is the major regulatory mechanism of p21, which induces p21 degradation. However, it is unclear whether ubiquitylated p21 can be recycled. In this study, we report USP11 as a deubiquitylase of p21. In the nucleus, USP11 binds to p21, catalyzes the removal of polyubiquitin chains conjugated onto p21, and stabilizes p21 protein...
April 16, 2018: Proceedings of the National Academy of Sciences of the United States of America
Xiaosong Zhi, Jun Xiong, Mengchao Wang, Hongxia Zhang, Gang Huang, Jian Zhao, Xiaoyuan Zi, Yi-Ping Hu
Induced hepatic stem cells (iHepSCs) have great potential as donors for liver cell therapy due to their self-renewal and bipotential differentiation properties. However, the efficiency of bidifferentiation and repopulation efficiency of iHepSCs is relatively low. Recent evidence shows that physiological hypoxia, a vital factor within stem cell "niche" microenvironment, plays key roles in regulating tissue stem cell biological behaviors including proliferation and differentiation. In this study, we found that physiological hypoxia (10% O2 ) enhanced the stemness properties and promoted the proliferation ability of iHepSCs by accelerating G1/S transition via p53-p21 signaling pathway...
2018: Oxidative Medicine and Cellular Longevity
Yupeng Wu, Yadong Wang, Ming Liu, Min Nie, Ying Wang, Yexuan Deng, Bing Yao, Tao Gui, Xinyu Li, Lingling Ma, Chan Guo, Chi Ma, Junyi Ju, Quan Zhao
Methylation of histone H4 lysine 20 (H4K20) has been associated with cancer. However, the functions of the histone methyltransferases that trigger histone H4K20 methylation in cancers, including suppressor of variegation 4-20 homolog 1 (Suv4-20h1), remain elusive. In the present study, it was demonstrated that the knockdown of the histone H4K20 methyltransferase Suv4-20h1 resulted in growth inhibition in chronic myeloid leukemia K562 cells. Disruption of Suv4-20h1 expression induced G1 arrest in the cell cycle and increased expression levels of cyclin dependent kinase inhibitor 1A (p21WAF1/CIP1 ), an essential cell cycle protein involved in checkpoint regulation...
May 2018: Oncology Letters
Wanhong Li, Chunjin Li, Shuxiong Chen, Lina Sun, Hongjiao Li, Lu Chen, Xu Zhou
Inhibins regulate folliculogenesis, gametogenesis and hormone secretion via endocrine, paracrine and autocrine manners, and play roles in encouraging or suppressing proliferation of cells. In order to investigate the effects of inhibin A on proliferation and apoptosis of porcine granulosa cells (GCs), GCs were isolated from ovarian follicles (3-6 mm), treated with inhibin A at different concentrations. The cell viability, mitochondrial membrane potential (MMP), expression of proliferation-related genes and cell cycle were detected...
March 26, 2018: Theriogenology
C Beinke, M Port, R Ullmann, K Gilbertz, M Majewski, M Abend
Dicentric chromosome analysis (DCA) is the gold standard for individual radiation dose assessment. However, DCA is limited by the time-consuming phytohemagglutinin (PHA)-mediated lymphocyte activation. In this study using human peripheral blood lymphocytes, we investigated PHA-associated whole genome gene expression changes to elucidate this process and sought to identify suitable gene targets as a means of meeting our long-term objective of accelerating cell cycle kinetics to reduce DCA culture time. Human peripheral whole blood from three healthy donors was separately cultured in RPMI/FCS/antibiotics with BrdU and PHA-M...
April 3, 2018: Radiation Research
Karnika Singh, Qin Dong, Prakash S TimiriShanmugam, Sweaty Koul, Hari K Koul
Current therapies in Pancreatic Cancer (PaCa) are ineffective due to deregulated cell cycle driven by landscape mutations. In this study, we show for the first time that tetrandrine (TET) inhibits proliferation of the PaCa cells and inhibits PaCa tumor growth. TET inhibits cell cycle transition at G1/S boundary. TET increased levels of p21Cip1/Waf1 and p27Kip1 , had no effect on the levels of CDK4/6 proteins and decreased the levels of cyclin D1 and pRb proteins. TET resulted in changes in mRNA levels of cyclin D1 and p21Cip1/Waf1 but had no effect on the mRNA of p27Kip1 ...
March 29, 2018: Cancer Letters
Paula Andrea Marin, Marcelo Santos da Silva, Raphael Souza Pavani, Carlos Renato Machado, Maria Carolina Elias
One of the most important mechanisms for repairing double-strand breaks (DSBs) in model eukaryotes is homologous recombination (HR). Although the genes involved in HR have been found in Trypanosoma brucei and studies have identified some of the proteins that participate in this HR pathway, the recruitment kinetics of the HR machinery onto DNA during DSB repair have not been clearly elucidated in this organism. Using immunofluorescence, protein DNA-bound assays, and DNA content analysis, we established the recruitment kinetics of the HR pathway in response to the DSBs generated by ionizing radiation (IR) in procyclic forms of T...
March 29, 2018: Scientific Reports
Chu-Fang Chou, Yu-Hua Hsieh, Clinton J Grubbs, Venkatram R Atigadda, James A Mobley, Reinhard Dummer, Donald D Muccio, Isao Eto, Craig A Elmets, W Timothy Garvey, Pi-Ling Chang
BACKGROUND: Bexarotene (Targretin® ) is currently the only FDA approved retinoid X receptor (RXR) -selective agonist for the treatment of cutaneous T-cell lymphomas (CTCLs). The main side effects of bexarotene are hypothyroidism and elevation of serum triglycerides (TGs). The novel RXR ligand, 9-cis UAB30 (UAB30) does not elevate serum TGs or induce hypothyroidism in normal subjects. OBJECTIVES: To assess preclinical efficacy and mechanism of action of UAB30 in the treatment of CTCLs and compare its action with bexarotene...
March 15, 2018: Journal of Dermatological Science
Pedro Nicolau-Neto, Antonio Palumbo, Marco De Martino, Francesco Esposito, Tatiana de Almeida Simão, Alfredo Fusco, Luiz Eurico Nasciutti, Nathalia Meireles Da Costa, Luis Felipe Ribeiro Pinto
FOXM1 (forkhead box protein M1) is a transcription factor that participates in all stages of tumor development, mainly through the control of cell cycle and proliferation, regulating the expression of genes involved in G1/S and G2/M transition and M phase progression. The ubiquitin conjugating enzyme E2 (UBE2C) is a member of the anaphase promoting complex/cyclosome, promoting the degradation of several target proteins along cell cycle progression, during metaphase/anaphase transition. FOXM1 and UBE2C have been found overexpressed in a wide range of different solid tumors...
March 29, 2018: Genes
Raghava Potula, Bijayesh Haldar, Jonathan M Cenna, Uma Sriram, Shongshan Fan
We and others have demonstrated that stimulants such as methamphetamine (METH) exerts immunosuppressive effects on the host's innate and adaptive immune systems and has profound immunological implications. Evaluation of the mechanisms responsible for T-cell immune dysregulation may lead to ways of regulating immune homeostasis during stimulant use. Here we evaluated the effects of METH on T cell cycle entry and progression following activation. Kinetic analyses of cell cycle progression of T-cell subsets exposed to METH demonstrated protracted G1/S phase transition and differentially regulated genes responsible for cell cycle regulation...
2018: Cell Death Discovery
Bei-Bei Su, Shu-Wei Zhou, Cai-Bin Gan, Xiao-Ning Zhang
Aims: MicroRNA-186 (miR-186) has been shown to be involved in various types of cancer. The purpose of this study was to investigate the expression level and functional role of miR-186 in human cutaneous malignant melanoma cells. Subjects and Methods: Expression of miR-186 was analyzed in human cutaneous malignant melanoma (CMM) cell lines SK-MEL-1, G-361, A375 and A875, and human normal epidermal melanocytes cell line HEMn-LP by quantitative reverse transcription polymerase chain reaction (qRT-PCR)...
2018: Journal of Cancer Research and Therapeutics
Jorge Fung-Uceda, Kyounghee Lee, Pil Joon Seo, Stefanie Polyn, Lieven De Veylder, Paloma Mas
The circadian clock and cell cycle as separate pathways have been well documented in plants. Elucidating whether these two oscillators are connected is critical for understanding plant growth. We found that a slow-running circadian clock decelerates the cell cycle and, conversely, a fast clock speeds it up. The clock component TOC1 safeguards the G1 -to-S transition and controls the timing of the mitotic cycle at early stages of leaf development. TOC1 also regulates somatic ploidy at later stages of leaf development and in hypocotyl cells...
March 19, 2018: Developmental Cell
M Flinck, S H Kramer, S F Pedersen
Precise spatiotemporal regulation of intracellular pH (pHi ) is a prerequisite for normal cell function, and changes in pHi or pericellular pH (pHe ) exert important signaling functions. It is well established that proliferation of mammalian cells is dependent on a permissive pHi in the slightly alkaline range (7.0-7.2). It is also clear that mitogen signaling in nominal absence of HCO3 - is associated with an intracellular alkalinization (~0.3 pH unit above steady state pHi ), which is secondary to activation of Na+ /H+ exchange...
March 25, 2018: Acta Physiologica
Dong-Qing Xu, Hidemi Toyoda, Lei Qi, Mari Morimoto, Ryo Hanaki, Shotaro Iwamoto, Yoshihiro Komada, Masahiro Hirayama
Mammalian target of rapamycin (mTOR) complex (mTORC) is frequently activated in diverse cancers. Although dual mTORC1/2 inhibitors are currently under development to treat various malignancies, the emergence of drug resistance has proven to be a major complication. AZD8055 is a novel, potent ATP-competitive and specific inhibitor of mTOR kinase activity, which blocks both mTORC1 and mTORC2 activation. In this study, we acquired AZD8055-resistant neuroblastoma (NB) cell sublines by using prolonged stepwise escalation of AZD8055 exposure (4-12 weeks)...
March 20, 2018: Biochemical and Biophysical Research Communications
Yuhuan Ma, Wenwei Zheng, Houhuang Chen, Xiang Shao, Pingdong Lin, Xianxiang Liu, Xihai Li, Hongzhi Ye
The present study investigated the mechanism underlying the effects of glucosamine (GlcN) on the proliferation of chondrocytes isolated from the knee cartilage of Sprague‑Dawley rats. Chondrocytes were treated with various concentrations of GlcN or without GlcN. The effects of GlcN on chondrocyte proliferation were determined using reverse transcription‑polymerase chain reaction, western blot analysis and immunohistochemistry. The results indicated that GlcN significantly improved chondrocyte viability, accelerated G1/S transition during progression of the cell cycle and promoted the expression of cell cycle regulatory proteins, including cyclin D1, cyclin‑dependent kinase (CDK)4 and CDK6, thus indicating that GlcN may promote chondrocyte proliferation...
March 22, 2018: International Journal of Molecular Medicine
Akito Nakamura, Daisuke Nakata, Yuichi Kakoi, Mihoko Kunitomo, Saomi Murai, Shunsuke Ebara, Akito Hata, Takahito Hara
The CDK8/19 kinase module comprises a subcomplex that interacts with the Mediator complex and regulates gene expression through phosphorylation of transcription factors and Mediator subunits. Mediator complex subunits have been increasingly implicated in cancer and other diseases. Although high expression of CDK8/19 has been demonstrated in prostate cancer, its function has not been thoroughly examined. Here we report that CDK8/19 modulates the gene expression of cell cycle regulators and thereby maintains the proper G1/S transition in prostate cancer cells...
March 2, 2018: Oncotarget
Deng-Qing Zhang, Jin-Song Li, Yu-Mei Zhang, Feng Gao, Ruo-Zhu Dai
AIMS: Astragaloside IV (AS-IV) is the central active component extracted from Radix astragali, an herbal remedy widely used in traditional Chinese medicine for the treatment of cardiovascular diseases. Aberrant proliferation of vascular smooth muscle cells (VSMCs) is closely involved in the initiation and progression of cardiovascular complications, such as atherosclerosis. Here we investigated whether AS-IV inhibited agonist-induced vascular smooth muscle cells (VSMCs) proliferation and the underlying mechanism...
March 19, 2018: Life Sciences
Ling Wang, Mengqing Li, Yuting Zhan, Xiaojiao Ban, Tingting Zeng, Yinghui Zhu, Jingping Yun, Xin-Yuan Guan, Yan Li
POTE ankyrin domain family, member G (poteg) belongs to POTE family. The POTE family is composed of many proteins which are very closely related and expressed in prostate, ovary, testis, and placenta. Some POTE paralogs are related with some cancers. Here we showed that down-regulation of POTEG was detected in about 60% primary esophageal squamous cell carcinoma (ESCC) tumor tissues. Clinical association studies determined that POTEG down-regulation was significantly correlated with tumor differentiation, lymph nodes metastasis and TNM staging...
March 22, 2018: Molecular Carcinogenesis
F-D Sun, P-C Wang, R-L Luan, S-H Zou, X Du
OBJECTIVE: Drug resistance has become an important factor that threatens the survival and prognosis of patients with breast cancer, especially in patients with advanced breast cancer. Several microRNAs have been proved to participate in the resistant process; however, the role of miR-574 in doxorubicin (Dox) resistant breast cancer is still unclear. PATIENTS AND METHODS: Quantitative Real-time poly chain reaction (qRT-PCR) was employed to detect the expression level of miR-574 in breast cancer Dox-resistant MCF-7/Adr cell line and parental MCF-7 cell line...
March 2018: European Review for Medical and Pharmacological Sciences
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