Emerging roles of the SUMO pathway in development.

Sumoylation is a reversible post-translational modification that targets a variety of proteins mainly within the nucleus, but also in the plasma membrane and cytoplasm of the cell. It controls diverse cellular mechanisms such as subcellular localization, protein-protein interactions, or transcription factor activity. In recent years, the use of several developmental model systems has unraveled many critical functions for the sumoylation system in the early life of diverse species. In particular, detailed analyses of mutant organisms in both the components of the SUMO pathway and their targets have established the importance of the SUMO system in early developmental processes, such as cell division, cell lineage commitment, specification, and/or differentiation. In addition, an increasing number of developmental proteins, including transcription factors and epigenetic regulators, have been identified as sumoylation substrates. Sumoylation acts on these targets through various mechanisms. For example, this modification has been involved in converting a transcription factor from an activator to a repressor or in regulating the localization and/or stability of numerous transcription factors. This review will summarize current information on the function of sumoylation in embryonic development in different species from yeast to mammals.

Coxsackievirus B5 induced apoptosis of HeLa cells: effects on p53 and SUMO.

Coxsackievirus B5 (CVB5), a human enterovirus of the family Picornaviridae, is a frequent cause of acute and chronic human diseases. The pathogenesis of enteroviral infections is not completely understood, and the fate of the CVB5-infected cell has a pivotal role in this process. We have investigated the CVB5-induced apoptosis of HeLa cells and found that it happens by the intrinsic pathway by a mechanism dependent on the ubiquitin-proteasome system, associated with nuclear aggregation of p53. Striking redistribution of both SUMO and UBC9 was noted at 4 h post-infection, simultaneously with a reduction in the levels of the ubiquitin-ligase HDM2. Taken together, these results suggest that CVB5 infection of HeLa cells elicit the intrinsic pathway of apoptosis by MDM2 degradation and p53 activation, destabilizing protein sumoylation, by a mechanism that is dependent on a functional ubiquitin-proteasome system.