scholarly journals SIRT7 Deacetylates STRAP to Regulate p53 Activity and Stability

2020 ◽  
Vol 21 (11) ◽  
pp. 4122 ◽  
Author(s):  
Miao Yu ◽  
Xiaoyan Shi ◽  
Mengmeng Ren ◽  
Lu Liu ◽  
Hao Qi ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Cell Death ◽  
Cell Cycle Arrest ◽  
Creb Binding Protein ◽  
Serine Threonine Kinase ◽  
Receptor Associated Protein ◽  
Threonine Kinase ◽  
P53 Signaling ◽  
Cycle Arrest

Serine-threonine kinase receptor-associated protein (STRAP) functions as a regulator of both TGF-β and p53 signaling that participates in the regulation of cell proliferation and cell death in response to various stresses. Here, we demonstrate that STRAP acetylation plays an important role in p53-mediated cell cycle arrest and apoptosis. STRAP is acetylated at lysines 147, 148, and 156 by the acetyltransferases CREB-binding protein (CBP) and that the acetylation is reversed by the deacetylase sirtuin7 (SIRT7). Hypo- or hyperacetylation mutations of STRAP at lysines 147, 148, and 156 (3KR or 3KQ) influence its activation and stabilization of p53. Moreover, following 5-fluorouracil (5-FU) treatment, STRAP is mobilized from the cytoplasm to the nucleus and promotes STRAP acetylation. Our finding on the regulation of STRAP links p53 with SIRT7 influencing p53 activity and stability.

scholarly journals Dual Roles of Serine-Threonine Kinase Receptor-Associated Protein (STRAP) in Redox-Sensitive Signaling Pathways Related to Cancer Development

2018 ◽  
Vol 2018 ◽  
pp. 1-9 ◽  
Author(s):  
Ravi Manoharan ◽  
Hyun-A Seong ◽  
Hyunjung Ha
Keyword(s):  
Cell Proliferation ◽  
Cell Death ◽  
Signaling Pathways ◽  
Intracellular Signaling ◽  
Transforming Growth Factor ◽  
Human Cancer ◽  
Tumor Formation ◽  
Serine Threonine Kinase ◽  
Receptor Associated Protein ◽  
Threonine Kinase

Serine-threonine kinase receptor-associated protein (STRAP) is a transforming growth factor β (TGF-β) receptor-interacting protein that has been implicated in both cell proliferation and cell death in response to various stresses. However, the precise roles of STRAP in these cellular processes are still unclear. The mechanisms by which STRAP controls both cell proliferation and cell death are now beginning to be unraveled. In addition to its biological roles, this review also focuses on the dual functions of STRAP in cancers displaying redox dysregulation, where it can behave as a tumor suppressor or an oncogene (i.e., it can either inhibit or promote tumor formation), depending on the cellular context. Further studies are needed to define the functions of STRAP and the redox-sensitive intracellular signaling pathways that enhance either cell proliferation or cell death in human cancer tissues, which may help in the development of effective treatments for cancer.

A Withanolide-rich Fraction of Athenaea velutina Induces Apoptosis and Cell Cycle Arrest in Melanoma B16F10 Cells

Planta Medica ◽  
2021 ◽  
Author(s):  
Alisson A. Almeida ◽  
Graziela D. A. Lima ◽  
Marinês Eiterer ◽  
Laís A. Rodrigues ◽  
Juliana A. do Vale ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Cell Death ◽  
Cell Cycle Arrest ◽  
Cancer Cell ◽  
Conservation Strategies ◽  
Migration And Invasion ◽  
In Vitro Tests ◽  
B16f10 Cells ◽  
Cycle Arrest

Abstract Athenaea velutina is a promising Brazilian shrub with cytotoxic and antimigratory properties against cancer cells. However, the mechanism of induction of cancer cell death and the compounds involved remain unknown. To ascertain these bioactive compounds, bioassay-guided fractionation was performed, alongside the appropriate in vitro tests. A withanolide-rich fraction (FAv_5) from the dichloromethane extract increased cytotoxic activity by 1.5-fold (IC50 = 2.1 µg/mL). Fourteen withanolide steroids were tentatively identified for the first time for this species by mass spectrometry coupled to liquid chromatography (LC MS/MS), including withanolide A, aurelianolide A, and aurelianolide B. FAv_5 significantly decreased cell proliferation, migration, and invasion with a selectivity index greater than 8 for B16F10 cells. Furthermore, flow cytometry with annexin V fluorescein isothiocyanate/propidium iodide (V-FITC/PI) staining showed FAv_5 to promote cell cycle arrest at the G0/G1-phase as well as apoptotic cell death. Overall, these findings highlight A. velutina as a source of withanolide-steroids that inhibit cancer cell proliferation through apoptosis and cell cycle blockade mechanisms. Details on the geographic distribution of A. velutina and species conservation strategies have also been highlighted.

P2Y11 impairs cell proliferation by induction of cell cycle arrest and sensitizes endothelial cells to cisplatin-induced cell death

2011 ◽  
Vol 112 (9) ◽  
pp. 2257-2265 ◽  
Author(s):  
Zhilin Xiao ◽  
Mei Yang ◽  
Qingshan Lv ◽  
Wenmeng Wang ◽  
Minjie Deng ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Endothelial Cells ◽  
Cell Death ◽  
Cell Cycle Arrest ◽  
Cycle Arrest

Inhibitor of growth 3 induces cell death by regulating cell proliferation, apoptosis and cell cycle arrest by blocking the PI3K/AKT pathway

2018 ◽  
Vol 25 (9-10) ◽  
pp. 240-247 ◽  
Author(s):  
Song Zhao ◽  
Long Wang ◽  
Chunmei Zhang ◽  
Yu Deng ◽  
Bai Zhao ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Cell Death ◽  
Cell Cycle Arrest ◽  
Akt Pathway ◽  
Cycle Arrest

scholarly journals Chemopreventive effects of pterostilbene through p53 and cell cycle in mouse lung of squamous cell carcinoma model

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Omchit Surien ◽  
Ahmad Rohi Ghazali ◽  
Siti Fathiah Masre
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Cell Death ◽  
Protein Expression ◽  
Cell Cycle Arrest ◽  
Mouse Lung ◽  
High Dose ◽  
Ki 67 ◽  
Cycle Arrest ◽  
Chemoprevention Agent

AbstractCell proliferation and cell death abnormalities are strongly linked to the development of cancer, including lung cancer. The purpose of this study was to investigate the effect of pterostilbene on cell proliferation and cell death via cell cycle arrest during the transition from G1 to S phase and the p53 pathway. A total of 24 female Balb/C mice were randomly categorized into four groups (n = 6): N-nitroso-tris-chloroethyl urea (NTCU) induced SCC of the lungs, vehicle control, low dose of 10 mg/kg PS + NTCU (PS10), and high dose of 50 mg/kg PS + NTCU (PS50). At week 26, all lungs were harvested for immunohistochemistry and Western blotting analysis. Ki-67 expression is significantly lower, while caspase-3 expression is significantly higher in PS10 and PS50 as compared to the NTCU (p < 0.05). There was a significant decrease in cyclin D1 and cyclin E2 protein expression in PS10 and PS50 when compared to the NTCU (p < 0.05). PS50 significantly increased p53, p21, and p27 protein expression when compared to NTCU (p < 0.05). Pterostilbene is a potential chemoprevention agent for lung SCC as it has the ability to upregulate the p53/p21 pathway, causing cell cycle arrest.

scholarly journals Transcriptional CDK inhibitors, CYC065 and THZ1 promote Bim-dependent apoptosis in primary and recurrent GBM through cell cycle arrest and Mcl-1 downregulation

2021 ◽  
Vol 12 (8) ◽  
Author(s):  
Viktorija Juric ◽  
Lance Hudson ◽  
Joanna Fay ◽  
Cathy E. Richards ◽  
Hanne Jahns ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Death ◽  
Cell Cycle Arrest ◽  
Cortical Neurons ◽  
Apoptotic Cell ◽  
Cdk Inhibitors ◽  
Induce Cell Death ◽  
Viability Loss ◽  
Cycle Arrest ◽  
Recurrent Gbm

AbstractActivation of cyclin-dependent kinases (CDKs) contributes to the uncontrolled proliferation of tumour cells. Genomic alterations that lead to the constitutive activation or overexpression of CDKs can support tumourigenesis including glioblastoma (GBM), the most common and aggressive primary brain tumour in adults. The incurability of GBM highlights the need to discover novel and more effective treatment options. Since CDKs 2, 7 and 9 were found to be overexpressed in GBM, we tested the therapeutic efficacy of two CDK inhibitors (CKIs) (CYC065 and THZ1) in a heterogeneous panel of GBM patient-derived cell lines (PDCLs) cultured as gliomaspheres, as preclinically relevant models. CYC065 and THZ1 treatments suppressed invasion and induced viability loss in the majority of gliomaspheres, irrespective of the mutational background of the GBM cases, but spared primary cortical neurons. Viability loss arose from G2/M cell cycle arrest following treatment and subsequent induction of apoptotic cell death. Treatment efficacies and treatment durations required to induce cell death were associated with proliferation velocities, and apoptosis induction correlated with complete abolishment of Mcl-1 expression, a cell cycle-regulated antiapoptotic Bcl-2 family member. GBM models generally appeared highly dependent on Mcl-1 expression for cell survival, as demonstrated by pharmacological Mcl-1 inhibition or depletion of Mcl-1 expression. Further analyses identified CKI-induced Mcl-1 loss as a prerequisite to establish conditions at which the BH3-only protein Bim can efficiently induce apoptosis, with cellular Bim amounts strongly correlating with treatment efficacy. CKIs reduced proliferation and promoted apoptosis also in chick embryo xenograft models of primary and recurrent GBM. Collectively, these studies highlight the potential of these novel CKIs to suppress growth and induce cell death of patient-derived GBM cultures in vitro and in vivo, warranting further clinical investigation.

scholarly journals Transcriptional network constituted of CBP, Ku70, NOX2, and BAX prevents the cell death of necrosis, paraptosis, and apoptosis in human melanoma

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Liang Ding ◽  
Yalei Wen ◽  
Xin Zhang ◽  
Fang Zhao ◽  
Kenao Lv ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Death ◽  
Apoptotic Cell ◽  
Human Melanoma ◽  
Transcriptional Network ◽  
Multiple Roles ◽  
Creb Binding Protein ◽  
Cycle Arrest ◽  
Intracellular Ros ◽  
High Level

AbstractCREB-binding protein (CBP) is an acetyltransferase known to play multiple roles in the transcriptions of genes involving oxidative metabolism, cell cycle, DNA damage checkpoints, and cell death. In this study, CBP was found to positively regulate the expression of Ku70, and both CBP and Ku70 were found to negatively regulate the expression of NOX2, therefore, mitigating the intracellular ROS in human melanoma. Knocking down CBP or Ku70 induced necrotic and paraptotic cell death as indicated by high-level intracellular ROS, cytoplasmic vacuolization, and cell cycle arrest in the S phase. In addition, chromosomal condensations were also observed in the cells proceeding necrotic and paraptotic cell death, which was found to be related to the BAX-associated intrinsic pathway of apoptotic cell death, when Ku70 was decreased either by CBP depletion or by Ku70 depletion directly. Our results, therefore, supported the idea that CBP, Ku70, BAX, and NOX2 have formed a transcriptional network in the prevention of cell death of necrosis, paraptosis, and apoptosis in human melanoma.

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