Sumoylation at the Host-Pathogen Interface

Wilson, Van G.

In contrast to K-bZIP, the adenovirus E1B-55K protein appears to be a SUMO1-specific SUMO ligase [74] . It was originally reported that E1B-55K enhanced p53 sumoylation in vivo but lacked SUMO ligase activity in vitro, suggesting that it might be recruiting a cellular ligase to the E1B-55K/p53 complex [75] . However, a subsequent study showed both in vivo and in vitro enhancement of p53 sumoylation confirming that E1B-55K is itself SUMO ligase [74] . This ligase activity may be specific to p53 as E1B-55K did not increase sumoylation of pRB [75] . Interestingly, E1B-55K is itself sumoylated at lysine 104, and mutation of this residue reduces ligase activity on p53. Pennella et al. found that this same SUMO conjugation site mutation also impaired E1B-55K association with PML NBs and the E1B-55K-dependent export of p53 to cytoplasmic aggresomes [74] . Additionally, they demonstrated that sumoylation of p53 reduced its intracellular mobility and increased its tethering to NBs resulting in enhanced nuclear export of p53. Based on these observations they proposed that the SUMO ligase activity of E1B-55K is a mechanism that contributes to repression of p53 function by increasing p53 sumoylation which facilitates the association of p53 with NBs and its subsequent export from the nucleus.