Autophagy and protein kinase RNA-like endoplasmic reticulum kinase (PERK)/eukaryotic initiation factor 2 alpha kinase (eIF2α) pathway protect ovarian cancer cells from metformin-induced apoptosis

2015 ◽  
Vol 55 (4) ◽  
pp. 346-356 ◽  
Author(s):  
Hee-sun Moon ◽  
Boyun Kim ◽  
HyeRan Gwak ◽  
Dong Hoon Suh ◽  
Yong Sang Song
Keyword(s):  
Ovarian Cancer ◽  
Endoplasmic Reticulum ◽  
Protein Kinase ◽  
Cancer Cells ◽  
Initiation Factor ◽  
Ovarian Cancer Cells ◽  
Eukaryotic Initiation Factor ◽  
Eukaryotic Initiation Factor 2 ◽  
Initiation Factor 2 ◽  
Induced Apoptosis

scholarly journals Eukaryotic initiation factor 3, subunit C silencing inhibits cell proliferation and promotes apoptosis in human ovarian cancer cells

2019 ◽  
Vol 39 (8) ◽  
Author(s):  
Fang Wen ◽  
Zhang-Ying Wu ◽  
Lei Nie ◽  
Qi-Zhu Zhang ◽  
Yuan-Kun Qin ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Molecular Mechanisms ◽  
Protein Translation ◽  
Initiation Factor ◽  
Ovarian Cancer Cells ◽  
Human Ovarian Cancer ◽  
Eukaryotic Initiation Factor ◽  
Translational Initiation

Abstract Ovarian cancer remains the leading cause of death among all gynaecological cancers, illustrating the urgent need to understand the molecular mechanisms involved in this disease. Eukaryotic initiation factor 3c (EIF3c) plays an important role in protein translation and cancer cell growth and proliferation, but its role in human ovarian cancer is unclear. Our results showed that EIF3c silencing significantly up-regulated 217 and down-regulated 340 genes. Ingenuity Pathway Analysis (IPA) indicated that the top differentially expressed genes are involved in ‘Classical Pathways’, ‘Diseases and Functions’ and ‘Networks’, especially those involved in signalling and cellular growth and proliferation. In addition, eIF3c silencing inhibited cellular proliferation, enhanced apoptosis and regulated the expression of apoptosis-associated proteins. In conclusion, these results indicate that by dysregulating translational initiation, eIF3c plays an important role in the proliferation and survival of human ovarian cancer cells. These results should provide experimental directions for further in-depth studies on important human ovarian cancer cell pathways.

scholarly journals Endoplasmic Reticulum Stress Decreases Intracellular Thyroid Hormone Activation via an eIF2a-Mediated Decrease in Type 2 Deiodinase Synthesis

2011 ◽  
Vol 25 (12) ◽  
pp. 2065-2075 ◽  
Author(s):  
Rafael Arrojo e Drigo ◽  
Tatiana L. Fonseca ◽  
Melany Castillo ◽  
Matthias Salathe ◽  
Gordana Simovic ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Endoplasmic Reticulum ◽  
Er Stress ◽  
Initiation Factor ◽  
Eukaryotic Initiation Factor ◽  
Human Airway ◽  
Eukaryotic Initiation Factor 2 ◽  
Initiation Factor 2 ◽  
In Cells

Abstract Cells respond rapidly to endoplasmic reticulum (ER) stress by blocking protein translation, increasing protein folding capacity, and accelerating degradation of unfolded proteins via ubiquitination and ER-associated degradation pathways. The ER resident type 2 deiodinase (D2) is normally ubiquitinated and degraded in the proteasome, a pathway that is accelerated by enzyme catalysis of T4 to T3. To test whether D2 is normally processed through ER-associated degradation, ER stress was induced in cells that endogenously express D2 by exposure to thapsigargin or tunicamycin. In all cell models, D2 activity was rapidly lost, to as low as of 30% of control activity, without affecting D2 mRNA levels; loss of about 40% of D2 activity and protein was also seen in human embryonic kidney 293 cells transiently expressing D2. In primary human airway cells with ER stress resulting from cystic fibrosis, D2 activity was absent. The rapid ER stress-induced loss of D2 resulted in decreased intracellular D2-mediated T3 production. ER stress-induced loss of D2 was prevented in the absence of T4, by blocking the proteasome with MG-132 or by treatment with chemical chaperones. Notably, ER stress did not alter D2 activity half-life but rather decreased D2 synthesis as assessed by induction of D2 mRNA and by [35S]methionine labeling. Remarkably, ER-stress-induced loss in D2 activity is prevented in cells transiently expressing an inactive eukaryotic initiation factor 2, indicating that this pathway mediates the loss of D2 activity. In conclusion, D2 is selectively lost during ER stress due to an eukaryotic initiation factor 2-mediated decrease in D2 synthesis and sustained proteasomal degradation. This explains the lack of D2 activity in primary human airway cells with ER stress resulting from cystic fibrosis.

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