A Nuclear Stress Pathway that Parallels Cytoplasmic Stress Granule Formation

Abstract

Summary Stress adaptation is exploited by cancer cells to survive and proliferate under adverse conditions. Survival pathways induced by stress are thus highly promising therapeutic targets. One key pathway involves formation of cytoplasmic stress granules, which regulate the location, stability, and translation of specific mRNAs. Here, we describe a transcriptional stress response that is triggered by similar stressors and characterized by accumulation of RepoMan (cell division cycle associated 2) at nuclear stress foci (nucSF). Formation of these structures is reversible, and they are distinct from known nuclear organelles and stress bodies. Immunofluorescence analysis revealed accumulation of heterochromatic markers, and increased association of RepoMan with the adenylate cyclase 2 (ADCY2) gene locus in stressed cells accompanied reduced levels of ADCY2 mRNA and protein. Quantitative comparison of the RepoMan interactome in stressed vs. unstressed cells identified condensin II as a nucSF factor, suggesting their functional association in the establishment and/or maintenance of these facultative heterochromatic domains.

Stress Granules Involved in Formation, Progression and Metastasis of Cancer: A Scoping Review

“…The percentage of various studies is shown in Figure 2. Meanwhile, the majority of studies, about 66% of studies, are dedicated to cell culture studies only (Baguet et al, 2007;Miyoshi et al, 2007;Arimoto et al, 2008;Eisinger-Mathason et al, 2008;Goulet et al, 2008;Busà et al, 2010;Gottschald et al, 2010;Guo et al, 2010;Kalra et al, 2010;Nikpour et al, 2011;Taniuchi et al, 2011aTaniuchi et al, ,b, 2014Park et al, 2012;Fournier et al, 2013;Pizzo et al, 2013;Thedieck et al, 2013;Chang et al, 2014;Kano et al, 2014;Podszywalow-Bartnicka et al, 2014;Yuan et al, 2014;Liu et al, 2015;Somasekharan et al, 2015;Szafron et al, 2015;Valentin-Vega et al, 2016;Weeks et al, 2016;Narayanan et al, 2017;Wall and Lewis, 2017;Takayama et al, 2018;Haghandish et al, 2019;Heberle et al, 2019;Kashiwagi et al, 2019;Mazloomian et al, 2019;Cui et al, 2020;Do et al, 2020;Brown et al, 2021).…”

“…The stages of metastasis can be summarized in the steps of local invasion, intravasation by blood/lymphatic circulation, and extravasation in new tissue and proliferation and angiogenesis, respectively (Figure 4; Shelton et al, 2010). Meanwhile, the stresses that enter the cancer cells push the situation in a direction to dysregulate the equilibrium of SGs and use SGs as an advantage in cancer conditions to benefit cancer cells (Anderson et al, 2015;Do et al, 2020).…”

CDK7/CDK9 mediates transcriptional activation to prime paraptosis in cancer cells

“…Alternatively, this also suggests in situ proteotoxic stress to recruit the effectors into the nucleus. Inhibition of eIF2α phosphorylation by trans-ISRIB and protein synthesis by CHX has been shown to reverse the accumulation of stress granules induced by arsenite but fails in nuclear stress foci formation [ 55 ].…”