p53 and Translation Attenuation Regulate Distinct Cell Cycle Checkpoints during Endoplasmic Reticulum (ER) Stress

Thomas, Sally E.; Malzer, Elke; Ordóñez, Adriana; Dalton, Louise; Wout, Emily F.A. van ′t; Liniker, Elizabeth; Crowther, Damian C.; Lomas, David A.; Marciniak, Stefan J.

doi:10.1074/jbc.m112.424655

Cited by 41 publications

(36 citation statements)

References 58 publications

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Section: Effects Of Er Stress Activators On Developmentmentioning

confidence: 99%

“…Cells may arrest either in G1 or G2 (Thomas, et al, 2013). G2 arrest is mediated downstream of PERK activation, through CHK1 activation, a potent cell cycle inhibitor also known for its activation in response to DNA damage (Malzer, et al, 2010, Thomas, et al, 2013). Cell cycle arrest in G1 occurs secondarily following activation of PERK, which can diminish synthesis of cyclin D1 (Brewer and Diehl, 2000, Thomas, et al, 2013).…”

Section: Effects Of Er Stress Activators On Developmentmentioning

confidence: 99%

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Stress signaling in mammalian oocytes and embryos: a basis for intervention and improvement of outcomes

Latham

2015

Cell Tissue Res

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Oocytes and early stage embryos are highly sensitive to variation in diverse exogenous factors such as temperature, osmolarity, oxygen, nutrient restriction, pH, shear stress, toxins, amino acid availability, and lipids. It is becoming increasingly apparent that many such factors negatively affect the endoplasmic reticulum, protein synthesis and protein processing, initiating ER stress and unfolded protein responses. As a result, ER stress signaling serves as a common mediator of cellular responses to diverse stressors. In oocytes and embryos, this leads to developmental arrest and epigenetic changes. Recent studies have revealed that preventing ER stress or inhibiting ER stress signaling can preserve or even enhance oocyte and embryo developmental potential. This chapter reviews ER stress signaling, how it arises, how it affects oocytes and embryos, and how its occurrence can be managed or prevented.

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Section: Effects Of Er Stress Activators On Developmentmentioning

confidence: 99%

Section: Effects Of Er Stress Activators On Developmentmentioning

confidence: 99%

Stress signaling in mammalian oocytes and embryos: a basis for intervention and improvement of outcomes

Latham

2015

Cell Tissue Res

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“…For example, a recent report provided evidence suggesting that UPR signaling modulates the function of a p53 isoform ( 122 ). In addition, ER stress may affect the cell cycle and protein translation in a p53-dependent manner ( 123,124 ). p53 is also a relevant mediator of ER stress-dependent apoptosis through the transcriptional upregulation of the BCL2 family members PUMA and NOXA ( 125 ), and, interestingly, p53-defi cient mice exhibit constitutive ER stress ( 120 ).…”

Section: Er Stress and Dna Damage/repairmentioning

confidence: 99%

“…Cross-talk between the UPR and p53 has been reported in many studies (see examples in refs. [122][123][124][125], which may infl uence gene expression toward cell adaptation or induction of apoptosis, and thus determine cancer cell fate. For example, a recent report provided evidence suggesting that UPR signaling modulates the function of a p53 isoform ( 122 ).…”

Section: Er Stress and Dna Damage/repairmentioning

confidence: 99%

Endoplasmic Reticulum Stress–Activated Cell Reprogramming in Oncogenesis

2015

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Stress induced by the accumulation of unfolded proteins in the endoplasmic reticulum (ER) is observed in many human diseases, including cancers. Cellular adaptation to ER stress is mediated by the unfolded protein response (UPR), which aims at restoring ER homeostasis. The UPR has emerged as a major pathway in remodeling cancer gene expression, thereby either preventing cell transformation or providing an advantage to transformed cells. UPR sensors are highly regulated by the formation of dynamic protein scaffolds, leading to integrated reprogramming of the cells. Herein, we describe the regulatory mechanisms underlying UPR signaling upon cell intrinsic or extrinsic challenges, and how they engage cell transformation programs and/or provide advantages to cancer cells, leading to enhanced aggressiveness or chemoresistance. We discuss the emerging crosstalk between the UPR and related metabolic processes to ensure maintenance of protein homeostasis and its impact on cell transformation and tumor growth.Signifi cance: ER stress signaling is dysregulated in many forms of cancer and contributes to tumor growth as a survival factor, in addition to modulating other disease-associated processes, including cell migration, cell transformation, and angiogenesis. Evidence for targeting the ER stress signaling pathway as an anticancer strategy is compelling, and novel agents that selectively inhibit the UPR have demonstrated preliminary evidence of preclinical effi cacy with an acceptable safety profi le. Cancer Discov; 5(6);

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“…Mild phenotypes have been observed when only one copy of the H99 locus remains[30–34] but homozygotic mutants abolish virtually all apoptosis [17–19, 35]. Conversely, induction of IAP-antagonists in response to DNA damage or stress (proteotoxicity, viral infection, etc) is mediated by p53, overexpression of which can be used to induce cell death[36, 37]. …”

Section: Methodsmentioning

confidence: 99%

Detection of Cell Death in Drosophila Tissues

Vasudevan

Ryoo

2016

Methods in Molecular Biology

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Drosophila has served as a particularly attractive model to study cell death due to the vast array of tools for genetic manipulation under defined spatial and temporal conditions in vivo as well as in cultured cells. These genetic methods have been well supplemented by enzymatic assays and a panel of antibodies recognizing cell death markers. This chapter discusses reporters, mutants and assays used by various laboratories to study cell death in the context of development and in response to external insults.

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p53 and Translation Attenuation Regulate Distinct Cell Cycle Checkpoints during Endoplasmic Reticulum (ER) Stress

Cited by 41 publications

References 58 publications

Stress signaling in mammalian oocytes and embryos: a basis for intervention and improvement of outcomes

Stress signaling in mammalian oocytes and embryos: a basis for intervention and improvement of outcomes

Endoplasmic Reticulum Stress–Activated Cell Reprogramming in Oncogenesis

Detection of Cell Death in Drosophila Tissues

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