USP37 Activators

USP37, a deubiquitinating enzyme that plays a critical role in various cellular processes, is regulated by a spectrum of chemical activators that influence its activity through different pathways. Forskolin, through the activation of adenylyl cyclase and subsequent increase in cAMP levels, indirectly activates USP37 by promoting PKA-mediated phosphorylation, a modification that enhances USP37 activity. Similarly, Trichostatin A and Sodium Butyrate enhance USP37's functional activity by inhibiting histone deacetylases, which increases histone acetylation and can lead to upregulated expression of the USP37 gene. Okadaic Acid, by blocking protein phosphatases that typically dephosphorylate proteins, ensures USP37 remains in an active phosphorylated state. Proteasome inhibitors like MG132 and Epoxomicin serve to increase the pool of ubiquitinated proteins, which are substrates for USP37, thereby heightening its enzymatic action. PMA activates PKC, which may phosphorylate regulatory proteins that modulate USP37 activity, and LY294002, by inhibiting the PI3K/AKT pathway, could trigger compensatory mechanisms that enhance USP37 activity.

Further contributing to the activation of USP37 are compounds that indirectly influence substrate availability or cellular signaling pathways. Rapamycin, as an mTOR inhibitor, may indirectly enhance USP37 activity by upregulating protein recycling mechanisms in response to inhibited cellular growth signaling. SB216763 inhibits GSK-3, leading to the increased presence of β-catenin, a known substrate of USP37, thereby potentially enhancing USP37's enzymatic function. Chloroquine disrupts lysosomal degradation, which may lead to elevated ubiquitinated protein levels, again augmenting USP37 activity due to increased substrate availability.