About the book
The ubiquitin-proteasome pathway (UPP) consists of ubiquitin, substate proteins, E1 enzymes, E2 enzymes, E3 enzymes, and proteasome. Ubiquitin is a highly conserved small proteins with 76 amino acids and about 8.5 kDa. E1 enzymes are ubiquitin-activating enzymes. E2 enzymes are ubiquitin-conjugating enzymes. E3 enzymes are ubiquitin ligases. The proteasome is a 26S protein complex, which contains one 20S core and two 19S lids. The UPP actually consists of a series of enzymatic reactions: E1 binds to ubiquitin in order to activate ubiquitin in ATP-dependent fashion, the activated ubiquitin is conjugated with E2, and then ubiquitin-conjugated E2 together with E3 ligases recognizes substrate proteins and covalently attaches ubiquitin (monomer or polyubiquitin chain) to substrate proteins (ubiquitinated proteins). Ubiquitinated proteins are then delivered to the proteasome for degradation into peptides or amino acids, which are further used for synthesis of new proteins. The mentioned substrate proteins include unneeded proteins and misfolded proteins within cells and tissues. Also, there are the deubiquitinating enzymes (DUB) that can remove the attached ubiquitin chain. Thus, ubiquitination / deubiquitination is a reversible processes. The UPP plays a crucial roles in degrading most of intracellular proteins and maintaining the balance between protein synthesis and degradation. Component changes in the UPP are associated with multiple pathophysiological processes, such as cancer and neurodengerative diseases. For example, mutated or overexpressed E3 ligases can act as oncogenes, while some E3 ligases and DUBs are also tumor suppressors. For example, the UPP is involved in synaptic function which regulates the nervous system. The UPP regulates multiple biological processes, including DNA repair, mitophagy, angiogenesis, RTK signaling, NF-kB signaling, and mitochondrial maintenance, which are dynamically regulated by ubiquitination. This book will focus on changes of UPP components, the methodology for studying UPP, protein ubiquitination, and applications of UPP in different diseases.