Exp Mol Med.  2003 Feb;35(1):1-7.

Conjugation and deconjugation of ubiquitin regulating the destiny of proteins

• Baek KH

Abstract

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.

Keyword

lymphocytes; protein processing; post-translational

MeSH Terms

Amino Acid Sequence
Animals
Conserved Sequence
Cytokines/metabolism
Enzyme Activation
Forecasting
Human
Lymphocytes/enzymology/*metabolism
Models, Biological
Molecular Sequence Data
Protein Processing, Post-Translational
Protein Structure, Tertiary
Proteins/chemistry/isolation & purification/*metabolism
Recombinant Fusion Proteins/metabolism
Signal Transduction
Ubiquitin/*metabolism