| Project I |
Deubiquitinating Enzymes
|
|
Hematopoietic cell growth and differentiation are regulated by cytokines that induce the expression of specific target genes. Some genes directly control mitogenesis. Others regulate intracellular proteolysis, allowing a cell to rapidly switch from one physiologic state to another. Ubiquitin mediated proteolysis is an important mechanism for regulating cellular progresses in all eukaryotic cells. Polybiquitinated proteins are recognized and degraded by the proteasome, a multi-subunit protein degradation complex. Recently, this mechanism has been implicated in a diverse assortment of processes, including cell cycle regulation, transcriptional activation, and antigen presentation.
A large superfamily of genes encoding deubiquitinating enzymes (ubps), has recently been identified. Ubps are ubiquitin-specific thiolproteases that cleave linear ubiquitin precursor proteins or post-translationally modified proteins containing isopeptide ubiquitin conjugates. The cellular function of the ubps is not well understood. Interestingly, ubps vary in length and structural complexitiy, suggesting considerable function diversity. Sequence comparison reveals three conserved domains that serve as the active site for the enzyme. DUB-1 and DUB-2 are deubiquitinating enzymes isolated by screening a murine genomic library and have a simple two exon structure. DUB-1 is an immediate early gene specifically induced by IL-3, and is expressed only in hematopoietic B-cell progenitor cells. DUB-2 is a T-cell specific immediate-early gene induced by IL-2. Therefore, characterizing and understanding of the DUB enzymes is critical for the understanding of their role in growth regulatory differentiation and mitogenic processes in hematopoietic cells. Given the specificity of DUB-1 for hematopoietic B-cell progenitor cells and DUB-2 specificity for T-cells, this research project will be extremely relevant to the understanding of leukomogenesis. 2001. 04. 18 Presentation at Cancer Research Institute (CRI) of Seoul National University |
