changes in protein profiles in bortezomib applied multiple myeloma ...

1.2.7.2. Biology of The Proteasome
The 26S Proteasome plays an essential role in the targeted degradation of
intracellular proteins which are responsible for regulating essential cellular functions,
such as cell-cycle control, cellular adhesion, proliferation, survival and apoptosis
(Matthews et al., 1989; Glickman and Ciechanover, 2002). Lots of studies carried out
using proteasome inhibitors have shown that the 26S proteasome takes charge in the
elimination of more than 80% of all cellular proteins (Zwickl et al., 1999).
The proteasome is a 2.5-MDa multi-catalytic proteinase complex present in the
cytoplasm and nucleus of all eukaryotic cells (Richardson et al., 2003). The primary
function of this complex is to degrade proteins which have been tagged with a poly-
ubiquitin chain (Adams, 2003; Wolf and Hilt, 2004).
Figure 1.8. Scheme of the 26S Proteasome
(Source: Mateos and Miguel, 2007; Roodman, 2009)
26S proteasome is a cylindrical complex comprised of a 20S catalytic core
capped at one or both ends by 19S regulatory subunits (Nussbaum et al., 1998;
Richardson et al., 2003; Voorhees et al., 2003; Blade et al., 2005) (Figure 1.8). The 19S
regulatory subunits are responsible for binding the poly-ubiquitin chain and cleaving it
from the protein substrate. They also contain 6 ATPases that are thought to play a key
role to denature the target protein and might deliver the substrate into the proteolytic
chamber in the 20S subunit (Zwickl et al., 1999). The 20S catalytic core consists of four
stacked rings; two outer α-rings that interact with the 19S subunit to check protein entry
into the 20S catalytic core, and two inner β-rings which makes up of seven β subunits.
20