Abstract
The ubiquitin-proteasome system controls almost all cellular processes by degrading regulatory proteins. The 26S proteasome is composed of 70 different subunits arranged in two sub-complexes, a 20S core particle (CP) and one or two 19S regulatory particles (RP). The proteolytic sites are sequestered inside the CP so that substrate proteins must be unfolded to reach the sites. The RP recognizes the polyubiquitin chains, deconjugates ubiquitin chains, unfolds substrate proteins, and translocates into the catalytic CP. To gain insights into the molecular mechanisms how the 26S proteasome degrades the ubiquitinated substrates, we established a novel method that ubiquitinates any favorable protein. By using this method, we found that Lys63-linked polyubiquitin chain, known as non-degrading signal, is efficiently promotes the substate degradation (Saeki et al, 2009, Embo J). Tightly folded proteins such as GFP are degraded slowly, suggesting that physicalproperty of the substrate itself is important for the proteasomal degradation. Recently, we also unravelled the assembly mechanism of the 19S RP, which involves four proteasome-specific chaperones (Saeki et al, 2009, Cell).
