Engineering responsiveness to cell culture stresses: Growth arrest and DNA damage gene 153 (GADD153) and the unfolded protein response (UPR) in NS0 myeloma cells

2006 ◽  
Vol 94 (3) ◽  
pp. 514-521 ◽  
Author(s):  
Renata E. Cudna ◽  
Alan J. Dickson
2019 ◽  
Vol 152 (2) ◽  
pp. 208-220 ◽  
Author(s):  
Anna M. Ziel ◽  
Kimberly Wolzak ◽  
Anna Nölle ◽  
Petrus J. Hoetjes ◽  
Ernesto Berenjeno‐Correa ◽  
...  

2020 ◽  
Author(s):  
Shaliny Ramachandran ◽  
Tiffany Ma ◽  
Natalie Ng ◽  
Iosifina P. Foskolou ◽  
Ming-Shih Hwang ◽  
...  

ABSTRACTThe levels of hypoxia associated with resistance to radiotherapy significantly impact cancer patient prognosis. These levels of hypoxia initiate a unique transcriptional response with the rapid activation of numerous transcription factors in a background of global repression of transcription. Here, we show that the biological response to radiobiological hypoxia includes the induction of the DNA/RNA helicase SETX. In the absence of hypoxia-induced SETX, R-loop levels increase, DNA damage accumulates, and DNA replication rates decrease. SETX plays a key role in protecting cells from DNA damage induced during transcription in hypoxia. Importantly, we show that the mechanism of SETX induction is reliant on the PERK/ATF4 arm of the unfolded protein response. These data not only highlight the unique cellular response to radiobiological hypoxia, which includes both a replication stress dependent DNA damage response and an unfolded protein response but uncover a novel link between these two distinct pathways.


Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 4348-4348
Author(s):  
Toshiaki Yujiri ◽  
Atsuko Tanimura ◽  
Kozo Tagami ◽  
Yukinori Nakamura ◽  
Yukio Tanizawa

Abstract Accumulation of unfolded or misfolded proteins within the endoplasmic reticulum triggers the unfolded protein response (UPR). Evidence from several studies suggests that the UPR is activated in various tumors and might play a crucial role in tumor growth. For example, in vitro activation of the UPR alters the sensitivity of tumor cells to chemotherapeutic agents. The role of the UPR in hematological malignancies remains unclear, however. We therefore used real-time RT-PCR to quantitatively assess expression of UPR-related genes in clinical samples [peripheral blood (PB), bone marrow (BM) and lymph node (LN)] from 9 newly diagnosed patients with acute myeloid leukemia (AML), 5 with acute lymphoid leukemia (ALL), 4 with multiple myeloma (MM), 12 with Non-Hodgkin’s lymphoma, 1 with Hodgkin’s lymphoma and 6 with infectious lymphadenopathy. Thirteen healthy controls were also examined. Evaluated was the mRNA expression of a spliced form of X-box DNA-binding protein (XBP1), ER degradation enhancing a-mannosidase-like protein (EDEM), C/EBP-homologous protein (CHOP) and glucose regulated protein 78 (GRP78). We found the transcription levels of all four of these genes to be significantly higher in leukemic blast cells and myeloma cells than in control BM cells or PB mononuclear cells. In particular, leukemic cells from Philadelphia chromosome-positive ALL and aggressive MM cells showed higher levels of UPR-related gene expression. Thus, activation of the UPR might be associated with the malignant characteristics of leukemia and myeloma. By contrast, expression of UPR-related genes was not increased in lymphoma cells compared to LN cells from the patients with infectious lymphadenopathy. The present study provides the first evidence that UPR-related genes are activated in acute leukemia and multiple myeloma cells. Thus, activation of the UPR might play an important role in the development and progression of some hematological malignancies. More comprehensive in vitro studies will be necessary to determine the magnitude of the role played by the UPR, to identify the most important components of the pathway, and to determine which stages of tumor development are regulated by the UPR.


Pathology ◽  
2016 ◽  
Vol 48 ◽  
pp. S73-S74
Author(s):  
Nicholas Nikesitch ◽  
Chang Tao ◽  
Ken Lai ◽  
Murray Killingsworth ◽  
Sunna Bae ◽  
...  

Oncotarget ◽  
2017 ◽  
Vol 8 (44) ◽  
pp. 76085-76098 ◽  
Author(s):  
Staci L. Haney ◽  
Cheryl Allen ◽  
Michelle L. Varney ◽  
Kaitlyn M. Dykstra ◽  
Eric R. Falcone ◽  
...  

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