Akt scaffold proteins: the key to controlling specificity of Akt signaling

2021 ◽  
Author(s):  
Fan Bao ◽  
Peiqi Hao ◽  
Su An ◽  
Yang Yang ◽  
Ying Liu ◽  
...  
Keyword(s):  
Cancer Therapy ◽  
Signaling Pathway ◽  
Essential Role ◽  
Akt Signaling ◽  
Scaffold Proteins ◽  
Akt Signaling Pathway ◽  
Akt Kinase ◽  
Proliferation And Apoptosis ◽  
Suitable Treatment ◽  
Membrane Bound

The PI3K-Akt signaling pathway plays an essential role in regulating cell proliferation and apoptosis. Akt kinase is at the center of this signaling pathway and interacts with a variety of proteins. Overexpression of Akt has been found in almost 80% of tumors, however, inhibiting Akt has serious clinical side effects so is not a suitable treatment for cancer. During recent years, Akt scaffold proteins have received increasing attention for their ability to regulate Akt signaling and have emerged as potential targets for cancer therapy. In this paper, we categorize AKT kinase scaffold proteins into four groups based on their cellular location: membrane-bound activator and inhibitor, cytoplasm, and endosome. We describe how these scaffolds interact with Akt kinase, how they affect AKT activity, and how they regulate the specificity of Akt signaling. We also discuss the clinical application of Akt-scaffold proteins as targets for cancer therapy.

HSP20 Exerts a Protective Effect on Preeclampsia by Regulating Function of Trophoblast Cells Via Akt Pathways

2018 ◽  
Vol 26 (7) ◽  
pp. 961-971 ◽  
Author(s):  
Fanfan Li ◽  
Yin Xie ◽  
Yuanyuan Wu ◽  
Mengzhou He ◽  
Meitao Yang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Signaling Pathway ◽  
Akt Signaling ◽  
Extravillous Trophoblast ◽  
Akt Signaling Pathway ◽  
Trophoblast Cells ◽  
Heat Shock Protein 20 ◽  
Apoptosis Index ◽  
Proliferation And Apoptosis ◽  
Associated Proteins

Preeclampsia (PE) remains the leading cause of maternal and fetal morbidity and mortality. Excessive apoptosis of the placenta and poor remodeling of spiral arteries caused by insufficient invasion of trophoblast cells into uterus have been implicated in the pathogenesis of PE. Accumulating evidence showed that heat shock protein 20 (HSP20) is closely associated with the proliferation, apoptosis, and metastasis of tumor cells. However, little is known about whether HSP20 plays a role in the development of PE. In this study, we detected the apoptosis index and the expressions of HSP20 and apoptosis-associated proteins in the placentas from PE and normal pregnancies. We found that HSP20 was reversely related to the apoptosis rate and the levels of proapoptotic proteins. Moreover, we identified that HSP20 could suppress the proliferation and apoptosis of trophoblast cells, turning them into a more invasive phenotype. Additionally, H2O2-induced oxidative stress was significantly alleviated, and several key proteins on the Akt signaling pathway were upregulated in HSP20-overexpressing trophoblast cells. These findings strongly suggested that HSP20 might play a role in the remodeling of spiral arteries through affecting the invasiveness of extravillous trophoblast cells via Akt signaling pathway, and the dysregulation of it might contribute to the pathophysiology of PE.

scholarly journals USP25 Regulates the Proliferation and Apoptosis of Ovarian Granulosa Cells in Polycystic Ovary Syndrome by Modulating the PI3K/AKT Pathway via Deubiquitinating PTEN

2021 ◽  
Vol 9 ◽  
Author(s):  
Yue Gao ◽  
Jiao Chen ◽  
Rui Ji ◽  
Jinli Ding ◽  
Yan Zhang ◽  
...  
Keyword(s):  
Mouse Model ◽  
Signaling Pathway ◽  
Granulosa Cells ◽  
Polycystic Ovary ◽  
Granular Cell ◽  
Akt Signaling ◽  
Pten Expression ◽  
Akt Signaling Pathway ◽  
Proliferation And Apoptosis ◽  
Major Factors

Background: Polycystic ovarian syndrome (PCOS) is an endocrine-related disease related to abnormal folliculogenesis and is a leading cause of infertility worldwide. Inhibition of granulosa cells (GCs) proliferation and increased GCs apoptosis have been identified as the major factors in aberrant follicle maturation.Methods: USP25 and PTEN expression in GCs from women with and without PCOS was analyzed using Western blotting. A PCOS-like mouse model was constructed using USP25 knockout and wild-type mice to explore the role of USP25 in PCOS. The human granular cell line KGN was cultured for proliferation and apoptosis assays, and the effect of USP25 on PTEN was investigated after transfection with shRNA-USP25 lentivirus.Results: USP25 expression was found to be elevated in patients and mice with PCOS. With mouse model, we observed a reduction in PCOS symptoms in mice after USP25 deletion. Increased proliferation, reduced apoptosis, activation of the phosphoinositide-3-kinase (PI3K)/protein kinase B (AKT) signaling pathway and decreased PTEN expression were found in KGN cells after USP25 knockdown. Finally, we verified that USP25 could deubiquitinate PTEN in KGN cells.Conclusions: In this study, we investigated that USP25 can regulate the PI3K/AKT signaling pathway by deubiquitinating PTEN, thus affecting the proliferation and apoptosis of GCs and contributing to the pathogenesis of PCOS.

Effects of microRNA-103 on the Proliferation and Apoptosis of Pancreatic Cancer Cells via Targeting Phosphatase and Tensin Homolog Deleted on Chromosome Ten (PTEN) and Activating Phosphoinositide 3-Kinase/A Serine/Threonine Kinase (PI3K/Akt) Signaling Pathway

2021 ◽  
Vol 11 (4) ◽  
pp. 690-696
Author(s):  
Xiaoyu Hai ◽  
Guozhong Zhao ◽  
Zhaolong Li ◽  
Junli Wu ◽  
Xiangzhao Xu ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Signaling Pathway ◽  
Cell Lines ◽  
Akt Signaling ◽  
Biological Database ◽  
Akt Signaling Pathway ◽  
Tensin Homolog ◽  
Pancreatic Cancer Cells ◽  
Proliferation And Apoptosis ◽  
Phenotype Formation

Objective: To investigate whether micro ribonucleic acid (miR)-103 affects pancreatic cancer (PaCa) cells via PTEN-activated PI3K/Akt signaling pathway. Methods: Differences in miR-103 expression in 35 pairs of PaCa tissues and cell lines (SW1990 and PATU8988S) were detected by RT-qPCR. miR-103 inhibitor was transfected into PaCa PATU8988S cell followed by analysis of proliferation and apoptosis of PaCa cells by MTT assay and flow cytometry, respectively. Results: MiR-103 exhibited a significantly high expression in PaCa tissues and cell lines (p < 0.05). Besides, the exogenous inhibition of miR-103 expression in PATU8988S cells significantly inhibited cell proliferation and migration but increased apoptosis activity (p < 0.05). According to the prediction of TargetScan biological database, miR-103 could bind PTEN 3′ untranslated region (3′UTR) and miR-103 was confirmed to suppress PTEN expression in a targeted way (p<0.05). Furthermore, down-regulation of PTEN activated PI3K/Akt signaling to affect the proliferation and apoptosis of PaCa cells (p < 0.05 or p <0.01). Conclusion: MiR-103 displays a significantly increased expression in PaCa cells and targets PTEN to activate PI3K/Akt signaling pathway, thus promoting malignant phenotype formation.

scholarly journals Marine compounds targeting the PI3K/Akt signaling pathway in cancer therapy

2020 ◽  
Vol 129 ◽  
pp. 110484 ◽  
Author(s):  
Jiaen Wei ◽  
Zhanping Gou ◽  
Ying Wen ◽  
Qiaohong Luo ◽  
Zunnan Huang
Keyword(s):  
Cancer Therapy ◽  
Signaling Pathway ◽  
Akt Signaling ◽  
Akt Signaling Pathway ◽  
Marine Compounds
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