Rpn11 抑制因子

Rpn11, a subunit of the 19S regulatory particle of the 26S proteasome, plays a pivotal role in the ubiquitin-proteasome pathway. The ubiquitin-proteasome system is a key cellular machinery responsible for the degradation of misfolded or redundant proteins. Proteins targeted for degradation are first tagged with multiple ubiquitin molecules, creating a polyubiquitin chain. Rpn11's primary role is in the deubiquitination process, where it functions as a metalloprotease, cleaving the isopeptide bond between the polyubiquitin chain and the substrate protein. This deubiquitination is a prerequisite for substrate proteins to be unfolded and threaded into the core particle of the proteasome for degradation. Given the essential nature of this process for cellular proteostasis, Rpn11 is considered a crucial component of the ubiquitin-proteasome system.

Rpn11 inhibitors are chemical entities that specifically target and modulate the enzymatic activity of Rpn11. These inhibitors interact with the active site of Rpn11, often coordinating with the metal ion essential for its protease activity, leading to an obstruction in the deubiquitination process. The inhibition of Rpn11's function impedes the subsequent degradation of substrate proteins, leading to an accumulation of polyubiquitinated proteins. Given the precision of these inhibitors in targeting a specific step in the protein degradation pathway, they provide an intricate tool for researchers to dissect the biochemical and cellular consequences of interrupted proteasomal processing. By studying the effects of Rpn11 inhibitors, scientists can glean a deeper understanding of cellular protein homeostasis and the ramifications of its disruption.