The SUMO stress response in transcriptional regulation: Causal relationships or secondary bystander effects?

Enserink, Jorrit M.

doi:10.1002/bies.202200065

Cited by 2 publications

(2 citation statements)

References 5 publications

(8 reference statements)

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“…Our observations align with the proposal that the SSR is primarily a consequence of altered transcription genome-wide, which involves a wave of transcription-mediated SUMO conjugation, and suggest that high levels of overall sumoylation do not play a protective role during these particular stresses. 17 , 27 In contrast, all tested strains with reduced Ubc9 activity, and consequently low sumoylation levels, showed growth defects when incubated at elevated temperatures, with most showing severe growth impairment. This is consistent with the finding that sumoylation facilitates heat tolerance in human cells and plants.…”

Section: Discussionmentioning

confidence: 93%

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Sumoylation is Largely Dispensable for Normal Growth but Facilitates Heat Tolerance in Yeast

Moallem

Akhter

Burke

et al. 2023

Molecular and Cellular Biology

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Numerous proteins are sumoylated in normally growing yeast and SUMO conjugation levels rise upon exposure to several stress conditions. We observe high levels of sumoylation also during early exponential growth and when nutrient-rich medium is used. However, we find that reduced sumoylation (∼75% less than normal) is remarkably well-tolerated, with no apparent growth defects under nonstress conditions or under osmotic, oxidative, or ethanol stresses. In contrast, strains with reduced activity of Ubc9, the sole SUMO conjugase, are temperature-sensitive, implicating sumoylation in the heat stress response, specifically. Aligned with this, a mild heat shock triggers increased sumoylation which requires functional levels of Ubc9, but likely also depends on decreased desumoylation, since heat shock reduces protein levels of Ulp1, the major SUMO protease. Furthermore, we find that a ubc9 mutant strain with only ∼5% of normal sumoylation levels shows a modest growth defect, has abnormal genomic distribution of RNA polymerase II (RNAPII), and displays a greatly expanded redistribution of RNAPII after heat shock. Together, our data implies that SUMO conjugations are largely dispensable under normal conditions, but a threshold level of Ubc9 activity is needed to maintain transcriptional control and to modulate the redistribution of RNAPII and promote survival when temperatures rise.

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Section: Discussionmentioning

confidence: 93%

“… 9 Sumoylation, therefore, does not appear to have general transcription-promoting or transcription-repressing roles, but instead, it likely controls expression of numerous genes in different ways. 7 , 9 , 17 , 18 …”

Section: Introductionmentioning

confidence: 99%

Sumoylation is Largely Dispensable for Normal Growth but Facilitates Heat Tolerance in Yeast

Moallem

Akhter

Burke

et al. 2023

Molecular and Cellular Biology

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Sumoylation is largely dispensable for normal growth but facilitates heat tolerance in yeast

Moallem

Akhter

Babu

et al. 2019

Preprint

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Sumoylation is an essential, conserved protein modification with hundreds of targets. Compared to the related modification ubiquitination, few enzymes are involved in SUMO conjugation and deconjugation, including a single conjugase, Ubc9, in yeast and mammals. This suggests that cells can simultaneously control the sumoylation level of numerous proteins by regulating just one enzyme of the SUMO pathway. Such modulated levels of cellular sumoylation are observed in response to a number of stress conditions, which typically cause a rapid and dramatic increase in overall sumoylation. Here, we demonstrate that ploidy, culture density, and nutrient availability also affect global sumoylation levels in yeast. To determine the effects of modulated cellular sumoylation on cell growth, we examined yeast strains that artificially display elevated or reduced sumoylation. Remarkably, reducing sumoylation levels by >70% has no effect on cell fitness, indicating that most SUMO conjugation events are not required for normal growth.Surprisingly, among a panel of stress conditions, only elevated temperatures severely impacted growth of cells harbouring constitutively low sumoylation levels. Consistent with the fact that Ubc9 and SUMO are essential, however, cells displaying less than ~5% of normal sumoylation levels show significantly impaired growth, even at normal temperatures. Finally, we demonstrate that many sumoylation events are highly transient, requiring constant de novo sumoylation to maintain steady state levels. Together, our results suggest that cells need only a low basal level of sumoylation for growth, but that normal levels are required pre-emptively to facilitate survival at elevated temperatures.

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The SUMO stress response in transcriptional regulation: Causal relationships or secondary bystander effects?

Cited by 2 publications

References 5 publications

Sumoylation is Largely Dispensable for Normal Growth but Facilitates Heat Tolerance in Yeast

Sumoylation is Largely Dispensable for Normal Growth but Facilitates Heat Tolerance in Yeast

Sumoylation is largely dispensable for normal growth but facilitates heat tolerance in yeast

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