KLHL11 Activators

Proteasome inhibitors such as Proteasome Inhibitor I, Bortezomib, MG132, Epoxomicin, Lactacystin, and Velcade directly prevent the breakdown of proteins by the ubiquitin-proteasome system. The inhibition of this system leads to an increase in the cellular concentration of proteins, including KLHL11, allowing it to maintain its cellular functions longer than it would under normal proteolytic conditions.

Other compounds, namely MLN4924, PYR-41, and IU1, interact with the ubiquitin-proteasome pathway but at different stages. MLN4924 disrupts the neddylation of cullin-RING ubiquitin ligases, which can result in a surge of protein stability across various substrates. PYR-41 targets the very start of the ubiquitination process, blocking the ubiquitin-activating enzyme E1 and potentially raising the levels of KLHL11 as a consequence. IU1, by inhibiting the deubiquitinase USP14, may lead to an accumulation of ubiquitinated forms of KLHL11, preventing its normal recycling and degradation. Chloroquine acts through a different mechanism as an autophagy inhibitor, potentially leading to the retention of KLHL11 by preventing its lysosomal degradation. This, along with ALLN's inhibition of calpain and proteasome activity, contributes to the same overarching effect of enhancing the presence of KLHL11 within the cell. LiCl inhibits GSK-3, a kinase involved in the ubiquitination and degradation of many proteins. By impeding this process, LiCl can contribute to a lesser turnover of KLHL11, increasing its stability and cellular activity.