Not all stresses are created equal, according to a pair of new studies, which shows that distinct ubiquitination patterns underlie cell recovery following different environmental stressors. Eukaryotic cells respond to environmental stressors - such as temperature extremes, exposure to toxins or damage, for example - through adaptive programs that help to ensure their survival, including the shutdown of key cellular processes. These responses are often associated with the formation of stress granules (SGs) - dense cytoplasmic aggregations of proteins and RNA - as well as with an increase in ubiquitination, a process that has long been thought to tag and induce the degradation of damaged or misfolded proteins that form during periods of cellular stress. However, while these measures are protective in the short term, their ability to be reversed is crucial so cells can return to normal after the stress has subsided. Yet, the molecular mechanisms involved in this reversal are not well understood. In a pair of studies, Brian Maxwell et al. and Youngdae Gwon et al. reveal new insights into the role of ubiquitination in the recovery of cellular activities following heat stress. Maxwell et al. examined which proteins become ubiquitinated during various types of cellular stress and found that different stresses elicited distinct ubiquitination patterns. What's more, for heat stress, they show that this ubiquitination primes cells to dismantle SGs and reinitiate normal cellular activities after stress has been removed. Building upon these findings, Gwon et al. show that the mechanism of SG disassembly is also dependent on the initiating stress. They find that, for heat-shocked cells, disassembly required the ubiquitination of G3BP1 - a central protein within the SG RNA-protein network. Gwon et al. also show that the mechanism through which SGs are disassembled is context-dependent as well - persistent SGs are degraded by autophagy, while short-lived granules undergo a different, autophagy-independent process. The findings from both studies are discussed further in a Perspective by Dorothee Dormann.
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Journal
Science