TY - JOUR
T1 - Phoslactomycin targets cysteine-269 of the protein phosphatase 2A catalytic subunit in cells
AU - Teruya, Takayuki
AU - Simizu, Siro
AU - Kanoh, Naoki
AU - Osada, Hiroyuki
N1 - Funding Information:
This study was supported in part by a Grant-in-Aid from the Ministry of Education, Culture, Sports, Science and Technology of Japan, and by the Chemical Biology Project (RIKEN). We thank Drs. T. Usui and Y. Sekiyama for their valuable discussions about this topic. We are also grateful to Y. Ichikawa and R. Nakazawa (Bioarchitect Research Group, RIKEN) for the DNA sequencing.
PY - 2005/4/25
Y1 - 2005/4/25
N2 - According to the chemical genetic approach, small molecules that bind directly to proteins are used to analyze protein function, thereby enabling the elucidation of complex mechanisms in mammal cells. Thus, it is very important to identify the molecular targets of compounds that induce a unique phenotype in a target cell. Phoslactomycin A (PLMA) is known to be a potent inhibitor of protein Ser/Thr phosphatase 2A (PP2A); however, the inhibitory mechanism of PP2A by PLMA has not yet been elucidated. Here, we demonstrated that PLMA directly binds to the PP2A catalytic subunit (PP2Ac) in cells by using biotinylated PLMA, and the PLMA-binding site was identified as the Cys-269 residue of PP2Ac. Moreover, we revealed that the Cys-269 contributes to the potent inhibition of PP2Ac activity by PLMA. These results suggest that PLMA is a PP2A-selective inhibitor and is therefore expected to be useful for future investigation of PP2A function in cells.
AB - According to the chemical genetic approach, small molecules that bind directly to proteins are used to analyze protein function, thereby enabling the elucidation of complex mechanisms in mammal cells. Thus, it is very important to identify the molecular targets of compounds that induce a unique phenotype in a target cell. Phoslactomycin A (PLMA) is known to be a potent inhibitor of protein Ser/Thr phosphatase 2A (PP2A); however, the inhibitory mechanism of PP2A by PLMA has not yet been elucidated. Here, we demonstrated that PLMA directly binds to the PP2A catalytic subunit (PP2Ac) in cells by using biotinylated PLMA, and the PLMA-binding site was identified as the Cys-269 residue of PP2Ac. Moreover, we revealed that the Cys-269 contributes to the potent inhibition of PP2Ac activity by PLMA. These results suggest that PLMA is a PP2A-selective inhibitor and is therefore expected to be useful for future investigation of PP2A function in cells.
KW - Chemical genetics
KW - Phoslactomycin
KW - Phosphatase
KW - Protein serine/threonine phosphatase 2A
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U2 - 10.1016/j.febslet.2005.03.049
DO - 10.1016/j.febslet.2005.03.049
M3 - Article
C2 - 15848189
AN - SCOPUS:17644377575
SN - 0014-5793
VL - 579
SP - 2463
EP - 2468
JO - FEBS Letters
JF - FEBS Letters
IS - 11
ER -