molecular trafficking
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Gut Microbes ◽  
2021 ◽  
Vol 13 (1) ◽  
pp. 1959841
Author(s):  
Seenivasan Boopathi ◽  
Danrui Liu ◽  
Ai-Qun Jia

2019 ◽  
Author(s):  
Kai-Yun Tsai ◽  
Zih-Yin Lai ◽  
Shing-Jyh Chang ◽  
Yung-Jen Chuang

Abstract Background p53 mutations are detected in up to 96% of high-grade serous ovarian carcinoma (HGSOC). Moreover, mutant p53 may cause oncogenic gain-of-function phenotypes in sustained activation of epidermal growth factor receptor (EGFR) signaling. In this study, we investigated whether p53 mutation could affect EGFR-related signaling and the corresponding therapeutic strategies in HGSOC.Methods For this study, we selected the p53 R248Q mutant (p53 R248Q ), which has the highest mutation frequency in ovarian cancer. Since we have previously demonstrated that the combined inhibition of EGFR and MDM2-p53 pathways by gefitinib and JNJ-26854165 exerts a strong synergistic lethal effect on p53-mutated HGSOC cells, the gefitinib and JNJ-26854165 responses in different p53 status cells were evaluated by cell viability and target protein expression assays.Results We showed that the phosphorylation of AKT, a critical molecule of EGFR downstream signaling, increased significantly when p53 R248Q was transiently overexpressed. Immunocytochemistry analysis further showed that upon p53 R248Q overexpression, several AKT-dependent mediators translocate in unique patterns within the cell. Subsequent analysis revealed that under the combined inhibition of gefitinib and JNJ-26854165, the cytonuclear trafficking of EGFR and MDM2 is disrupted. Moreover, when we further compared gefitinib and JNJ-26854165 responses in different p53 status cells, we found that the sensitivity to the single- or combined-inhibition treatments is also altered in p53 R248Q -overexpressing cells.Conclusions Our findings suggest that the R248Q mutation of p53 causes significant changes in signaling transduction, molecular trafficking and drug responses, which help to advance our understanding of p53 and to improve therapeutic strategies for HGSOC.


2018 ◽  
Vol 60 (4) ◽  
pp. 738-751 ◽  
Author(s):  
Munenori Kitagawa ◽  
Takumi Tomoi ◽  
Tomoki Fukushima ◽  
Yoichi Sakata ◽  
Mayuko Sato ◽  
...  

2016 ◽  
Vol 138 (18) ◽  
pp. 5745-5748 ◽  
Author(s):  
Jesús del Barrio ◽  
Seán T. J. Ryan ◽  
Pablo G. Jambrina ◽  
Edina Rosta ◽  
Oren A. Scherman

Aging Cell ◽  
2011 ◽  
Vol 10 (5) ◽  
pp. 832-843 ◽  
Author(s):  
Pasquale Picone ◽  
Daniela Giacomazza ◽  
Valeria Vetri ◽  
Rita Carrotta ◽  
Valeria Militello ◽  
...  

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