scholarly journals HIV-1 Vif up-regulates the expression of Tat via AKT Signaling pathway: Role of deubiquitinase USP17 and NQO1

2021 ◽  
Author(s):  
Sneh Lata ◽  
Vikas Sood ◽  
Akhil Banerjea
Keyword(s):  
Signaling Pathway ◽  
Akt Signaling ◽  
Dependent Manner ◽  
Tat Protein ◽  
Akt Signaling Pathway ◽  
Restriction Factors ◽  
Independent Manner ◽  
Host Restriction ◽  
Downstream Target ◽  
Hiv 1

Abstract Human Immunodeficiency Virus-1 (HIV-1) has a small RNA genome and depends on host cellular machinery for most of its activities. Host cellular proteins modulate the expression and activity of viral proteins to combat the virus. HIV-1 proteins are known to regulate each other for the benefit of virus by exploiting these modulations. Here, we report that HIV-1 Vif increases the expression of Tat via AKT signaling pathway. We show that HIV-1 Vif activates AKT signaling pathway by inducing phosphorylation of AKT. Mdm2, downstream target of AKT signaling, increases the expression of Tat protein in ubiquitin-independent manner by up-regulating NQO1 as well as in ubiquitin-dependent manner by inducing the expression levels of USP17 which is a deubiquitinase (DUB) and stabilizes Tat protein. Thus, HIV-1 proteins exploit AKT signaling pathway to escape host restriction factors and promote viral replication.

Corrigendum to “Proline-rich Akt substrate of 40 kDa (PRAS40): A novel downstream target of PI3k/Akt signaling pathway” [Cell. Signal. 2012; 24:17–24]

2012 ◽  
Vol 24 (11) ◽  
pp. 2226 ◽  
Author(s):  
Haitao Wang ◽  
Qishan Zhang ◽  
Qiang Wen ◽  
Yongxin Zheng ◽  
Philip Lazarovici ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Akt Signaling ◽  
Akt Signaling Pathway ◽  
Downstream Target ◽  
Cell Signal

scholarly journals Staurosporine suppresses survival of HepG2 cancer cells through Omi/HtrA2-mediated inhibition of PI3K/Akt signaling pathway

Tumor Biology ◽  
2017 ◽  
Vol 39 (3) ◽  
pp. 101042831769431 ◽  
Author(s):  
Youming Ding ◽  
Bin Wang ◽  
Xiaoyan Chen ◽  
Yu Zhou ◽  
Jianhui Ge
Keyword(s):  
Cell Death ◽  
Cell Viability ◽  
Cancer Cells ◽  
Signaling Pathway ◽  
Human Cancer ◽  
Akt Signaling ◽  
Therapeutic Effects ◽  
Concomitant Treatment ◽  
Dependent Manner ◽  
Akt Signaling Pathway

Staurosporine, which is an inhibitor of a broad spectrum of protein kinases, has shown cytotoxicity on several human cancer cells. However, the underlying mechanism is not well understood. In this study, we examined whether and how this compound has an inhibitory action on phosphatidylinositol 3-kinase (PI3K)/Akt pathway in vitro using HepG2 human hepatocellular carcinoma cell line. Cell viability and apoptosis were determined using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and terminal deoxyribonucleotidyl transferase–mediated dUTP-digoxigenin nick end labeling (TUNEL) assay, respectively. Glutathione S-transferase (GST) pull-down assay and co-immunoprecipitation were performed to detect protein–protein interactions. Small interfering RNA (siRNA) was used to silence the expression of targeted protein. We found that staurosporine significantly decreased cell viability and increased cell apoptosis in a concentration- and time-dependent manner in HepG2 cancer cells, along with the decreased expressions of PDK1 protein and Akt phosphorylation. Staurosporine was also found to enhance Omi/HtrA2 release from mitochondria. Furthermore, Omi/HtrA2 directly bound to PDK1. Pharmacological and genetic inhibition of Omi/HtrA2 restored protein levels of PDK1 and protected HepG2 cancer cells from staurosporine-induced cell death. In addition, staurosporine was found to activate autophagy. However, inhibition of autophagy exacerbated cell death under concomitant treatment with staurosporine. Taken together, our results indicate that staurosporine induced cytotoxicity response by inhibiting PI3K/Akt signaling pathway through Omi/HtrA2-mediated PDK1 degradation, and the process provides a novel mechanism by which staurosporine produces its therapeutic effects.

scholarly journals Androgen Plays a Carcinogenic Role in EOC via the PI3K/AKT Signaling Pathway in an AR-Dependent Manner

2021 ◽  
Vol 12 (6) ◽  
pp. 1815-1825
Author(s):  
Yanfang Li ◽  
Sha Li ◽  
Yizhou Zhang ◽  
Shuhong Shi ◽  
Shan Qin ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Akt Signaling ◽  
Dependent Manner ◽  
Akt Signaling Pathway

scholarly journals Parthenolide Augments the Chemosensitivity of Non-small-Cell Lung Cancer to Cisplatin via the PI3K/AKT Signaling Pathway

2021 ◽  
Vol 8 ◽  
Author(s):  
Li-Mei Wu ◽  
Xiao-Zhong Liao ◽  
Yan Zhang ◽  
Zi-Rui He ◽  
Shi-Qing Nie ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Signaling Pathway ◽  
Cell Lung Cancer ◽  
Caspase 3 ◽  
Akt Signaling ◽  
Small Cell ◽  
Dependent Manner ◽  
Akt Signaling Pathway ◽  
Small Cell Lung

The mortality rate of non-small-cell lung cancer (NSCLC) remains high worldwide. Although cisplatin-based chemotherapy may greatly enhance patient prognosis, chemotherapy resistance remains an obstacle to curing patients with NSCLC. Therefore, overcoming drug resistance is the main route to successful treatment, and combinatorial strategies may have considerable clinical value in this effort. In this study, we observed that both parthenolide (PTL) and cisplatin (DDP) inhibited the growth of NSCLC cells in a dose- and time-dependent manner. The combination of PTL and DDP presented a synergistic inhibitory effect on NSCLC at a ratio of 50:1. The combination of PTL and DDP synergistically inhibited cell migration and invasion, inhibited cell cycle progression, and induced apoptosis of A549 and PC9 cells. Bioinformatics and network pharmacology analysis indicated that PTL may primarily affect the phosphatidylinositol 3-kinase (PI3K)-AKT signaling pathway. After treatment with PTL and DDP either alone or in combination, Western blot analysis revealed that the proteins levels of Bax and cleaved Caspase-3 were upregulated, while p-PI3K, p-Akt, Caspase-3, and Bcl-2 proteins were downregulated. Among these alterations, the combination of PTL and DDP was found to exhibit the most significant effects. PTL might therefore be considered as a new option for combination therapy of NSCLC.

scholarly journals Effect of Eriodictyol on Retinoblastoma via the PI3K/Akt Pathway

2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Shu Wen ◽  
Meng Hu ◽  
Yan Xiong
Keyword(s):  
Anticancer Activity ◽  
Signaling Pathway ◽  
Vision Loss ◽  
Akt Signaling ◽  
Migration And Invasion ◽  
Dependent Manner ◽  
Akt Signaling Pathway ◽  
Anticancer Effects ◽  
Induced Apoptosis ◽  
Y79 Cells

Retinoblastoma (RB) is one of the most common intraocular malignancies in children, which causes vision loss and even threatens life. Eriodictyol is a natural flavonoid with strong anticancer activity. Some studies have shown that eriodictyol exerts anticancer effects in glioma, colon cancer, and lung cancer; however, no studies have reported the anticancer effects of eriodictyol on RB. Therefore, the aim of this study was to investigate the anticancer activity of eriodictyol against the RB Y79 cell line and its potential mechanism of action. Interestingly, we found that eriodictyol inhibited the proliferation, migration, and invasion of Y79 cells in a dose-dependent manner and decreased the expression of MMP-2 and MMP-9 proteins in the cells. In addition, eriodictyol-induced apoptosis in Y79 cells was assessed by flow cytometry and immunoblotting. Here, our study revealed that eriodictyol dose dependently inhibited the activation of the PI3K/Akt signaling pathway. Notably, the effect of eriodictyol on RB apoptosis was reversed by a PI3K agonist 740 Y-P. In conclusion, our study shows that eriodictyol effectively inhibits proliferation, migration, and invasion and induces apoptosis in RB cell lines, which may be the result of blocking the PI3K/Akt signaling pathway. Thus, eriodictyol may provide a new theoretical basis for exploring targeted antitumor natural therapies.

scholarly journals Effects of Rhizopus Nigricans Exopolysaccharide on Proliferation, Apoptosis, and Migration of Breast Cancer MCF-7 Cells and Akt Signaling Pathway

2021 ◽  
Vol 2021 ◽  
pp. 1-6
Author(s):  
Aizhai Xiang ◽  
Chen Ling ◽  
Wei Zhang ◽  
Honggang Chen
Keyword(s):  
Breast Cancer ◽  
Signaling Pathway ◽  
Akt Signaling ◽  
Migration And Invasion ◽  
Dependent Manner ◽  
Akt Signaling Pathway ◽  
Rhizopus Nigricans ◽  
And Migration ◽  
The Impact ◽  
Mcf 7

Objective. To study the effect of Rhizopus nigricans exopolysaccharide EPS1-1 on the proliferation, apoptosis, and migration of breast cancer MCF-7 cells. Methods. Human breast cancer MCF-7 cells were cultured in vitro and treated with different concentrations of EPS1-1. The effect of EPS1-1 on cell proliferation was tested by the CCK-8 experiment, and the effect of EPS1-1 on cell apoptosis was determined by flow cytometry. And the scratch test was used to detect the impact of EPS1-1 on cell migration. Western blot then was used to measure the expression changes of related proteins in the Akt signaling pathway. Results. Compared with the control group, treatment with EPS1-1 significantly reduced the proliferation, migration, and invasion ability of MCF-7 cells and promoted the apoptosis of MCF-7 cells in a dose-dependent manner. In terms of the underlying mechanism, EPS1-1 can significantly inhibit the phosphorylation of Akt at threonine 308 and serine 473 and cause the expression changes of downstream proliferation-related genes CCND1 and p21, apoptosis-related genes Bcl-2 and Bax, and migration-related genes Vimentin and E-cadherin in terms of their protein levels. Conclusion. EPS1-1 can inhibit the proliferation, migration, and invasion of breast cancer MCF-7 cells and promote the apoptosis of MCF-7 cells by inhibiting the activation of the Akt signaling pathway. Therefore, EPS1-1 can be used as a potential new drug or adjuvant drug for the treatment of breast cancer.

Dehydrocostus Lactone Inhibits Proliferation, Antiapoptosis, and Invasion of Cervical Cancer Cells Through PI3K/Akt Signaling Pathway

2015 ◽  
Vol 25 (7) ◽  
pp. 1179-1186 ◽  
Author(s):  
Enping Jiang ◽  
Xiwen Sun ◽  
Haixian Kang ◽  
Liping Sun ◽  
Weifang An ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Cancer Cells ◽  
Signaling Pathway ◽  
Specific Inhibitor ◽  
Akt Signaling ◽  
Dependent Manner ◽  
Akt Signaling Pathway ◽  
Cervical Cancer Cells ◽  
Dehydrocostus Lactone

ObjectivesRecent studies found that dehydrocostus lactone (DHC), a traditional Chinese medicine in curing chronic ulcer and inflammation, can inhibit several type of tumor cells. The purpose of this study was to define the role of DHC on cervical cancer cells and to explore its mechanism of action.MethodsWe used DHC alone or in combination with PI3K/Akt-specific inhibitor LY294002 (LY) to treat Hela cells [human papillomavirus (HPV)-18 positive] and C33a cells (HPV negative). The proliferation, apoptosis, and Akt activation were assessed. Cell invasive ability was assayed in transwell chambers.ResultsWe found that DHC significantly inhibited proliferation, antiapoptosis, and invasion of both cells, and reduced the level of p-Akt phosphorylation in these cells, in a dose- or time-dependent manner. In addition, these inhibitions of DHC were significantly strengthened by LY.ConclusionsThe result suggested that DHC plays a potent role in anticervical cancer in multiple biological aspects through PI3K/Akt signaling pathway, independently of HPV infection. This finding surely adds new knowledge to understand the role of DHC in fighting cancers.

Sign in / Sign up

Export Citation Format

Share Document