Open AccessDephosphorylation of Bcl‐2 by protein phosphatase 2A results in apoptosis resistance
Author(s) -
Simizu Siro,
Tamura Yuki,
Osada Hiroyuki
Publication year - 2004
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/j.1349-7006.2004.tb02214.x
Subject(s) - dephosphorylation , phosphorylation , protein phosphatase 2 , phosphatase , apoptosis , biology , protein phosphorylation , cell culture , phosphoric monoester hydrolases , cancer research , microbiology and biotechnology , chemistry , biochemistry , protein kinase a , genetics
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.