Premium
Prevention of p53 Degradation in Human MCF‐7 Cells by Proteasome Inhibitors Does Not Mimic the Action of Roscovitine
Author(s) -
RANFTLER CARMEN,
GUEORGUIEVA MARIETA,
WȨSIERSKAGA̧DEK JÒZEFA
Publication year - 2006
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1196/annals.1378.026
Subject(s) - proteasome , mcf 7 , regulator , downregulation and upregulation , proteasome inhibitor , protein degradation , microbiology and biotechnology , cancer research , kinase , chemistry , cancer cell , biology , cancer , biochemistry , human breast , gene , genetics
We have recently observed activation of wild‐type (wt) p53 protein in human MCF‐7 breast cancer cells upon treatment with roscovitine (ROSC), a potent cyclin‐dependent kinase inhibitor. It has been previously suggested that ROSC repressed transcription of Mdm‐2, a negative p53 regulator, and that the lack of Mdm‐2 contributes to the ROSC‐induced upregulation of p53 protein. Therefore, we decided to see whether the prevention of p53 degradation by proteasome inhibitors will mimic the effects generated by ROSC. Exposure of human MCF‐7 cells to different proteasome inhibitors resulted in a time‐dependent increase of p53. However, unlike ROSC, they failed to modify p53 protein at Ser46 and to induce p53AIP1 protein. Moreover, whereas ROSC arrested MCF‐7 cells in the G2‐phase of the cell cycle, proteasome inhibitors blocked cells primarily in the S‐phase, presumably because of the prevention of cyclin degradation. Our results indicate that prevention of p53 degradation by proteasome inhibitors does not mimic the action of ROSC.