Conjugation and deconjugation of ubiquitin regulating the destiny of proteins.
The homeostasis for a number of cellular proteins is regulated by not only phosphorylation and dephosphorylation, but also ubiquitination and deubiquitination. A number of proteins involved in the degradation of polypeptides have been isolated in various eukaryotic organisms from Saccharomyces cerevisiae to human. Recently, several deubiquitinating enzymes, classified into either the Ub C-terminal hydrolase (UCH) or the Ub-specific processing protease (UBP), have been reported. It has been shown that they contain conserved domains including Cys, His, and Asp residues throughout the enzyme. These proteins have been demonstrated that Cys and His domains are critical for deubiquitinating enzymatic activity. Recently, we have shown that the Asp domain localized between Cys and His domains is also essential for cleaving the ubiquitin from protein substrates. Mouse deubiquitinating enzymes including DUB-1, DUB-2, and DUB-2A have been isolated and they showed the expression specificity. Of these, DUB- 1 and DUB-2 are expressed in lymphocytes depending on the presence of cytokines (interleukin-3 in B-lymphocytes and interleukin-2 in T- lymphocytes, respectively), indicating that they are involved in cytokine signaling pathways. Isolation of all putative DUBs will help to identify their substrates and to regulate the homeostasis of cellular proteins, especially in proliferative cells.
Baek
Kwang-Hyun
KH
Department of Microbiology College of Medicine, Pochon CHA University Cell and Gene Therapy Research Institute CHA General Hospital, Seoul 135-081, Korea. baek@cha.ac.kr
D000595:Amino Acid Sequence; D000818:Animals; D017124:Conserved Sequence; D016207:Cytokines / Q000378:metabolism; D004789:Enzyme Activation; D005544:Forecasting; D006801:Humans; D008214:Lymphocytes / Q000201:enzymology / Q000378:metabolism*; D008954:Models, Biological; D008969:Molecular Sequence Data; D011499:Protein Processing, Post-Translational; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D015398:Signal Transduction; D025801:Ubiquitin / Q000378:metabolism*
D016207:Cytokines; D011506:Proteins; D011993:Recombinant Fusion Proteins; D025801:Ubiquitin