Since cantharidin is a potent and selective inhibitor of
PP2A (8), it is supposed to be functionally associated with phosphorylation activity.
Both agents are known protein phosphatase 1 (PP1) and protein phosphatase 2A (
PP2A) inhibitors [5].
These stress kinases are targets of
PP2A [98-100], a redox-sensitive protein phosphatase inactivated in an oxidized environment.
In cell culture experiments with mouse nerve cells, the researchers showed that metformin directly protects
PP2A against degradation by preventing the binding to special degradation proteins.
Their inherent capability for inhibiting serine/threonine-specific protein phosphatases (PPs; e.g., PP1,
PP2A, PP4, PP5) via covalent binding to the PP catalytic subunit (Hastie et al.
Una fosfatasa
PP2A esta tambien involucrada en la degradacion del complejo [beta]-catenina inhibiendo la senalizacion de Wnt a traves de APC y de la axina (50).
Inhibition of the Ser-Thr phosphatases PP1 and
PP2A by naturally occurring toxins.
Protein phosphatase 2A (
PP2A) is a multimeric enzyme that contains a scaffolding A subunit, a regulatory B subunit, and a catalytic C subunit [18].
Thornhill et al., "Biguanide metformin acts on tau phosphorylation via mTOR/protein phosphatase 2A (
PP2A) signaling," Proceedings of the National Academy of Sciences of the United States of America, vol.
The phosphorylation status and activity of Aurora-B are modulated by PP1 and
PP2A phosphatases; depending on the regulatory subunit they are bound to, these enzymes can directly modulate Aurora-B activity through dephosphorylation or they may dephosphorylate Aurora-B substrates [38].