Deubiquitinating polyubiquitin

Why are there so many DUBs and how do they achieve specificity The numerous DUBs identified to date suggest that DUBs have specifically evolved to act on distinct cellular substrates rather than to have general deubiquitinating activity (see Figure 8.1). We can ask what common features of these enzymes define them as DUBs and what differences allow specific DUBs to act on mono- vs. polyubiquitin How have they evolved to cleave only ISG15 or SUMO-modified substrates, for instance A body of data has been accumulated that at least partially answers these questions. 

S. M., and Eisenman, R. N., Histone deacetylase 6 binds polyubiquitin through its zinc finger (PAZ domain) and copurifies with deubiquitinating enzymes, Proc. Natl. Acad. Scl USA, 2002, 99, 13425. 

Figure 7 Multiple roles of the deubiquitinating enzymes. Deubiquitinating enzymes (DUBs) of the UCH type (dark scissors) process ubiquitin precursors. UCH-L1 generates monoubiquitins from tandemly linked ubiquitin gene product. UCH-L3 acts on ubiquitin synthesized as a protein fused to small ribosomal subunits. DUBs of the UBP type (shaded scissors) process ubiquitins linked in isopeptide linkage in polyubiquitin chains. DUBs also reverse the ubiquitination on erroneously targeted substrates (editing). Another important function of DUBs is disassembly of polyubiquitin chains as the ubiquitinated substrate is degraded. Ubiquitin attached to substrates after activation are indicated as lollipop-like structures with filled circles. Free ubiquitin or ubiquitin unit in precursor is shown with open circles.

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