dFoxo Dependent Transcription of the Heat Shock Proteins

Donovan, Marissa; Marr, Michael T.

doi:10.1096/fasebj.29.1_supplement.880.31

Cited by 2 publications

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“…In addition to SG formation, oxidative stresses regulate transcription factors such as FOXO, HSF1, and Nrf2 to induce changes in the cellular transcriptome ( Fedoroff, 2006 ; Donovan and Marr, 2015 ; Vihervaara et al. , 2018 ; Doonan et al.…”

Section: Introductionmentioning

confidence: 99%

The transcriptional response to oxidative stress is independent of stress-granule formation

Singh

Kandi

Jayaprakashappa

et al. 2022

MBoC

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Cells respond to stress with translational arrest, robust transcriptional changes, and transcription-independent formation of mRNP assemblies termed stress granules (SGs). Despite considerable interest in the role of SGs in oxidative, unfolded-protein and viral stress responses, whether and how SGs contribute to stress-induced transcription has not been rigorously examined. To address this, we characterized transcriptional changes in Drosophila S2 cells induced by acute oxidative-stress and assessed how these were altered under conditions that disrupted SG assembly. Oxidative stress for 3-hours predominantly resulted in induction or upregulation of stress-responsive mRNAs whose levels peaked during recovery after stress cessation. The stress-transcriptome is enriched in mRNAs coding for chaperones, including HSP70s, small heat shock proteins, glutathione transferases, and several non-coding RNAs. Oxidative stress also induced cytoplasmic SGs that disassembled 3-hours after stress cessation. As expected, RNAi-mediated knockdown of the conserved G3BP1/Rasputin protein inhibited SG assembly. However, this disruption had no significant effect on the stress-induced transcriptional response or stress-induced translational arrest. Thus, SG assembly and stress-induced gene expression alterations appear to be driven by distinctive signaling processes. We suggest that while SG assembly represents a fast, transient mechanism, the transcriptional response enables a slower, longer-lasting mechanism for adaptation to and recovery from cell stress.

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Section: Introductionmentioning

confidence: 99%

The transcriptional response to oxidative stress is independent of stress-granule formation

Singh

Kandi

Jayaprakashappa

et al. 2022

MBoC

View full text Add to dashboard Cite

show abstract

The Transcriptional Response to Oxidative Stress Is Independent of Stress-Granule Formation

Singh

Kandi

Jayaprakashappa

et al. 2021

Preprint

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Cells respond to stress with translational arrest, robust transcriptional changes, and transcription-independent formation of mRNP assemblies termed stress granules (SGs). Despite considerable interest in the role of SGs in oxidative, unfolded-protein, and viral stress responses, whether and how SGs contribute to stress-induced transcription has not been rigorously examined. To address this issue, we characterized transcriptional changes in Drosophila S2 cells induced by acute oxidative-stress and assessed how these were altered under conditions that disrupted SG assembly. Sodium-arsenite stress for 3 hours predominantly resulted in the induction or upregulation of stress-responsive mRNAs whose levels peaked during cell recovery after stress cessation. The stress-transcriptome is enriched in mRNAs coding for protein chaperones, including HSP70 and low molecular-weight heat shock proteins, glutathione transferases, and several non-coding RNAs. Oxidative stress also induced prominent cytoplasmic stress granules that disassembled 3-hours after stress cessation. As expected, RNAi-mediated knockdown of the conserved G3BP1/ Rasputin protein inhibited stress-granule assembly. However, this disruption had no significant effect on the stress-induced transcriptional response or stress-induced translational arrest. Thus, SG assembly and stress-induced effects on gene expression appear to be driven by distinctive signaling processes. We suggest that while SG assembly represents a fast, transient mechanism, the transcriptional response enables a slower, longer-lasting mechanism for adaptation to and recovery from cell stress.

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dFoxo Dependent Transcription of the Heat Shock Proteins

Cited by 2 publications

References 0 publications

The transcriptional response to oxidative stress is independent of stress-granule formation

The transcriptional response to oxidative stress is independent of stress-granule formation

The Transcriptional Response to Oxidative Stress Is Independent of Stress-Granule Formation

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