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.
Gomes
Rogério
R
Department of Cell Biology, University of São Paulo School of Medicine at Ribeirão Preto, Av. dos Bandeirantes, 3900, 14049-900, SP, Brazil. roggomes@usp.br
Guerra-Sá
Renata
R
Arruda
Eurico
E
D017209:Apoptosis / Q000502:physiology; D002467:Cell Nucleus / Q000502:physiology; D003384:Coxsackievirus Infections / Q000821:virology*; D045304:Cytochromes c / Q000378:metabolism; D029822:Enterovirus B, Human / Q000502:physiology*; D006367:HeLa Cells / Q000821:virology; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000502:physiology; D046988:Proteasome Endopeptidase Complex / Q000502:physiology; D025842:SUMO-1 Protein / Q000502:physiology*; D016159:Tumor Suppressor Protein p53 / Q000502:physiology*; D044763:Ubiquitin-Conjugating Enzymes / Q000502:physiology; D000098843:Ubiquitin-Conjugating Enzyme UBC9
D025842:SUMO-1 Protein; D016159:Tumor Suppressor Protein p53; D045304:Cytochromes c; D044763:Ubiquitin-Conjugating Enzymes; D046988:Proteasome Endopeptidase Complex; D000098843:Ubiquitin-Conjugating Enzyme UBC9