PP2A-δ Inibitori

I comuni inibitori di PP2A-δ includono, ma non solo, l'acido okadaico CAS 78111-17-8, la calicolina A CAS 101932-71-2, la cantaridina CAS 56-25-7, l'endotall CAS 145-73-3 e la fostriecina CAS 87860-39-7.

Chemical inhibitors of PP2A-δ can act through a variety of mechanisms to prevent its role in protein de-phosphorylation. Okadaic acid, for example, is a potent inhibitor that achieves this by binding directly to the catalytic subunit of PP2A-δ, which is essential for its activity. This binding prevents PP2A-δ from interacting with its substrates, thus keeping the protein in a phosphorylated state. Similarly, Calyculin A inhibits PP2A-δ by interacting with its catalytic site, blocking enzyme activity. Cantharidin also binds covalently to the catalytic subunit of PP2A-δ, providing another example of a direct inhibitor that prevents the de-phosphorylation process essential for PP2A-δ function. Endothall contributes to this inhibitory effect by mimicking the transition state of de-phosphorylation and blocking substrate access to the active site of PP2A-δ.

In addition to these direct inhibitors, other chemicals such as ionomycin may indirectly inhibit PP2A-δ by increasing intracellular calcium levels, which in turn may affect the regulatory B subunits that are part of the regulatory mechanism of PP2A-δ. Demeculcin disrupts microtubule polymerization, which in turn can affect PP2A-δ signaling pathways that are critical for cell cycle control. By disrupting these pathways, demecolcin can indirectly lead to the inhibition of PP2A-δ function. Fostriecin, Tautomycin, and Microcystin-LR are other examples that target the active site of PP2A-δ, binding directly to hinder its phosphatase activity. This also occurs with phenylarsin oxide, which interferes with catalytic function by interacting with vicinal dithiols within the catalytic subunit of PP2A-δ. Nodularin and cylindrospermopsin inhibit PP2A-δ in a manner similar to okadaic acid and microcystin-LR, binding to the active site and preventing protein de-phosphorylation, resulting in functional inhibition of the PP2A-δ protein itself. These different but specific chemical interactions collectively contribute to the functional inhibition of PP2A-δ, each affecting the activity of the protein through a unique biochemical interaction or cellular process.