Dephosphorylation of Bcl-2 by protein phosphatase 2A results in apoptosis resistance.
The anti-apoptotic protein, Bcl-2 was phosphorylated at the Ser-87 residue in normal human blood cells, while it was not phosphorylated in tumor cells. We identified protein phosphatase 2A (PP2A) as a Bcl-2-associated phosphatase that is responsible for dephosphorylation of Bcl-2 in tumor cell lines. Treatment of the tumor cells with a PP2A inhibitor resulted in the appearance of Bcl-2 phosphorylation at Ser-87. This observation suggests that Bcl-2 is constitutively phosphorylated, but is immediately dephosphorylated by PP2A in tumors. Phosphorylation of Bcl-2 protein at the Ser-87 residue resulted in a reduction in anti-apoptotic function in human tumor cell lines. Thus, not only the expression level, but also the dephosphorylation status may have important implications for the oncogenic activity of Bcl-2.
Simizu
Siro
S
Antibiotics Laboratory, Discovery Research Institute, RIKEN, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan.
Tamura
Yuki
Y
Osada
Hiroyuki
H
D017209:Apoptosis / Q000502:physiology*; D001773:Blood Cells / Q000378:metabolism; D015153:Blotting, Western; D045744:Cell Line, Tumor; D006801:Humans; D010749:Phosphoprotein Phosphatases / Q000378:metabolism*; D010766:Phosphorylation; D054648:Protein Phosphatase 2; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*
D019253:Proto-Oncogene Proteins c-bcl-2; D010749:Phosphoprotein Phosphatases; D054648:Protein Phosphatase 2