| Summary: | 博士 === 國立中山大學 === 生物醫學研究所 === 104 === p38 mitogen-activated protein kinase (MAPK) is of the essence in the cell’s response to environmental stresses, cytokines and DNA damage. p38 is distributed both in the cytosol and nucleus, and cytosolic p38 translocates into the nucleus in response to various stimuli, yet the exact mechanisms remain largely unclear. One response to cellular stress is the elevated expression of SUMO proteins. SUMOs have many roles in cellular biology including promoting nuclear translocalization. In our study, we have demonstrated that exposure of human cells to Helicobacter pylori (Hp) induces the expression of SUMOs and the activation of p38. A non-covalent interaction between SUMOs and both non-phosphorylated and phosphorylated p38 (p38 and p-p38) was identified, and the interaction was found to be SUMO concentration dependent. We found that upon Hp stimulation cytosolic p38 could be translocated into the nucleus by both SUMO-1 and SUMO-2, although both p38 and p-p38 have a stronger binding affinity for SUMO-2 than for SUMO-1. Mutation of SUMO interacting motif 3 (SIM3) of p38 abolished its binding to SUMOs and decreased SUMO-dependent nuclear transfer of p38. This study demonstrates that SUMOs serve as novel regulators of p38 and p-p38 nuclear translocation through a non-covalent SUMO-p38 interaction, independent of the phosphorylation state of p38.
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