USP19 Activators

USP19 (Ubiquitin-Specific Protease 19), a deubiquitinating enzyme (DUB) may be activated through cellular processes and pathways associated with ubiquitination and deubiquitination that ultimately influence USP19's function indirectly. One notable compound in this category is PR-619. PR-619 is a potent deubiquitinase (DUB) inhibitor, functioning as a broad-spectrum blocker of DUB activity. Although it does not activate USP19 directly, PR-619 plays a crucial role in impeding the removal of ubiquitin molecules from target proteins, leading to the accumulation of ubiquitinated substrates. This accumulation can impact cellular signaling pathways and protein turnover, providing valuable insights into the regulatory roles of USP19 within the ubiquitin-proteasome system.

Another strategy involves the use of MG-132. MG-132 works by blocking proteasomal degradation, which indirectly affects the levels of ubiquitinated proteins in cells. As USP19 is involved in regulating protein quality control and the removal of ubiquitin from specific substrates, inhibiting proteasomal degradation with MG-132 can lead to the stabilization of ubiquitinated proteins. This stabilization can help researchers investigate the substrates and cellular processes influenced by USP19. Additionally, the modulation of autophagy through compounds like Rapamycin presents another indirect approach. Rapamycin induces autophagy, a process that entails the degradation of cellular components, including ubiquitinated proteins. By influencing autophagy, Rapamycin indirectly affects the cellular environment, impacting the substrates and pathways under the regulation of USP19.