Polyubiquitin-chain-binding Proteins

In summary, despite emerging evidence that certain polyubiquitinated proteins are targeted to the 26S proteasome by carrier proteins, additional molecular details will be required for verification of this attractive model. These details include the marmer in which specific substrates are selected by different polyubiquitin-chain-binding proteins, and how the substrates are transferred from these proteins to PA700. 

---

Seibenhener ML, Babu JR, Geetha T et al. (2004) Sequestosome l/p62 is a polyubiquitin chain binding protein involved in ubiquitin proteasome degradation. Mol Cell Biol 24, 8055-8068. 

Despite the initial indication that Rpnl0/S5a was the polyubiquitin-chain-binding subunit of the 26S proteasome, subsequent studies showed that it cannot be the principal recognition element for this process. First, disruption of the Rpnl0/S5a gene in yeast is not lethal and inhibits the degradation of only a sub-class of ubiquitinated proteins [39]. Likewise, RNA interference-inhibited ex-... 

Ubiquitin-protein ligases promote not only the attachment of ubiquitin to the protein substrates but also the extension of the ubiquitin chain. What determines the choice between mono- vs. polyubiquitination is not well understood. It is possible that certain E3s catalyze only mono-ubiquitination. Alternatively, factors other than E3s might be responsible for the attachment of a single ubiquitin. Eor example, ubiquitin-binding accessory proteins have been suggested to block extension of the ubiquitin chain [25], whereas E3-associated ubiquitin hydrolase could trim down the polyubiquitin chain. The identification and characterization of ubiquitin E2 variant proteins (UEVs) have provided an explanation for the assembly of K63-linked polyubiquitin chains [26, 27]. As discussed later, UEVs can be considered as special E3s, with the ubiquitin chain as their substrates. 

Russell, N. S. and Wilkinson, K. D. Identification of a novel 29-linked polyubiquitin binding protein, ufd3, using polyubiquitin chain analogues. Biochemistry, 2004, 43, 4844-54. 

After the linkage of Ub to the substrate protein, a polyubiquitin (multiubiquitin) chain is often formed, in which the C-terminus of each ubiquitin unit is linked to a specific Lys residue (most commonly Lys48) of the previous Ub. The multiubiquitin-chain assembly is a processive reaction that usually requires only El, E2 and E3. However, an efficient multiubiquitination needs an additional conjugation factor termed E4 enzyme (Hoppe, 2005). Ubiquitin-protein ligases are, directly or indirectly, those that bind specific protein substrates, promote the transfer of Ub, and form a thioester intermediate to amide linkages with proteins or polyubiquitin chains. 

---