부산대학교 도서관

The functional diversity of the tumor suppressor protein p53 is mainly regulated by protein interactions. In this study, we describe a new interaction with the peptidyl-prolyl cis/trans isomerase cyclophilin 18 (Cyp18). The interaction reduced the sequence-specific DNA binding of p53 in vitro, whereas the inhibition of the interaction increased p53-reporter gene activity in vivo. The active site of the folding helper enzyme Cyp18 was directly involved in binding. The proline-rich region (amino acids 64–91) of p53 was most likely responsible for the observed binding because a synthetic peptide comprising amino acids 68–81 of p53 inhibited this interaction, and a p53 variant containing a proline residue at position 72 (p53P72) interacted with Cyp18 more effectively than the corresponding p53R72 variant. Impairment of the Cyp18–p53 interaction induced an accumulation of cells in the G2/M phase of the cell cycle, which was more pronounced when p53P72 was expressed compared with p53R72 in an otherwise isogenic cellular background. Moreover, p53-dependent apoptosis was elevated in Cyp18 knockout cells, suggesting an antiapoptotic potential of Cyp18–p53 complexes. Functional in vivo data hint to a possible clinical relevance of the p53–Cyp18 interaction observed. [ABSTRACT FROM AUTHOR]