Sumo and the cellular stress response
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REVIEW
Open Access
Sumo and the cellular stress response Jorrit M. Enserink
Abstract The ubiquitin family member Sumo has important functions in many cellular processes including DNA repair, transcription and cell division. Numerous studies have shown that Sumo is essential for maintaining cell homeostasis when the cell encounters endogenous or environmental stress, such as osmotic stress, hypoxia, heat shock, genotoxic stress, and nutrient stress. Regulation of transcription is a key component of the Sumo stress response, and multiple mechanisms have been described by which Sumo can regulate transcription. Although many individual substrates have been described that are sumoylated during the Sumo stress response, an emerging concept is modification of entire complexes or pathways by Sumo. This review focuses on the function and regulation of Sumo during the stress response. Keywords: Sumo, Stress response, Transcription, DNA damage response, ER stress, Viral infections, Nutrient stress, SIMs
Introduction Several small ubiquitin-like molecules were identified during the 1990s, including Sumo (Small ubiquitin-like modifier) [1]. Despite limited sequence similarity, Sumo is structurally related to ubiquitin with a similar protein fold. [2], although the distribution of charged residues on the surface of the Sumo molecule differs from that of ubiquitin [3]. The budding yeast Saccharomyces cerevisiae only expresses a single form of Sumo (encoded by the SMT3 gene), whereas mammalian cells express four; Sumo1, −2,-3,-4. During recent years it has become clear that Sumo has important functions in normal cell homeostasis, in large part through regulation of transcription (reviewed in Chymkowitch et al., submitted). However, Sumo is also very important for the cellular stress response, and many cellular stresses result in increased formation of Sumo conjugates. Sumo can be covalently attached to a large number of proteins to regulate their fate, localization and function. The physiological significance of many of these sumoylation events remains unknown, which is in part due to the fact that Sumo can be attached to multiple components of an entire complex, and preventing the attachment of Sumo to a single component of the complex often has little or no clear effect. Furthermore, when a given Sumo site is mutated, Sumo is sometimes Correspondence: [email protected] Institute for Microbiology, Oslo University Hospital, Sognsvannsveien 20N-0027, Oslo, Norway
attached to other sites in the same substrate with apparently little effect on the overall outcome. In contrast to the ubiquitination machinery, the sumoylation machinery only consists of very few components, raising the question how specificity is achieved and how the activity of the Sumo pathway is regulated. The scope of this review is to provide an overview of the function of Sumo in the cellular stress response, in particular transcription, and to highlight a number of key questions that remain to be answered.
Protein sumoylation The sumoylation mac
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