Proteasome regulator

I 7 7 Proteasome Regulator, PA700 (19S Regulatory Particle) Tab. n.1. Component Subunits of PA700/19S RP. 

S. A. The 19S complex of the proteasome regulates nucleotide excision repair in yeast. Genes. Dev. 2001, 15, 1528-1539. 

Bortezomib. Bortezomib (Velcade) inhibits pro-teasome activity in mammalian cells.11 Mammalian proteasome is responsible for degrading certain cellular proteins affecting cell function and division. By prolonging the activity of these proteins, bortezomib brings about complex changes in cell function that lead to cell dysfunction and death. Certain types of cancer, such as multiple myeloma, are more sensitive to impaired proteasome regulation, hence the use of this drug in these cancers. 

Proteasome regulators Lithocholic acid derivatives 3a-0-Pimeloyl-lithocholic acid methyl ester Isosteric isomer... 

Dang Z, Jung K, Qian K, Lee KH, Huang L, Chen CH (2012) Synthesis oflithocholic acid derivatives as proteasome regulators. ACS Med Chem Lett 3 925-930... 

Other mechanisms of proteasomal regulation are known such as the expression of three new subunits in the immune response, several phosphorylation sites for the 20S proteasome as well for the proteasomal regulators [20], the activation by poly-ADP-ribose polymerase [22], and some authors have suggested the presence of proteasome inhibitors. 

Bortezomib (velcade) (1R)-3-methyl-l-[[(2S)-1 -oxo-3-phenyl-2-[pyrazinylcarbonyl)amino] propyl]butyl]boronic acid binds to the 20S core of the 26S proteasome and reversibly inhibits its chymotrypsin-like activity. Inhibition of the proteasome disrupts multiple signaling cascades within the cell, often leading to cell death. The most important consequences of proteasome inhibition are believed to result from downregulation of NF-kB, a key transcription factor that promotes cell survival. In a similar manner, bortezomib disrupts ubiquitin-proteasome regulation of p2I, p27, and p53, which are key regulatory proteins in the cell cycle and initiators of apoptosis. 

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