Ubiquitin hydrolase

Jensen, D. E., et al., BAPl a novel ubiquitin hydrolase which binds to the BRCAl RING finger and enhances BRCAl-mediated cell growth suppression. Oncogene, 1998, 16(9), 1097-112. 

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. 

When looking at the examples shown in Figure 12.1, or at the large set of proteins not shown here, two general trends are obvious (i) the ubiquitin domain tends to be localized at the extreme N-terminus, and (ii) the host protein is typically involved in the ubiquitin system. The first observation has been interpreted as an evolutionary remnant of earlier ubiquitin-fusion proteins [40]. As mentioned above, ubiquitin is typically expressed as a precursor protein, wherein the ubiquitin moiety is localized at the N -terminus and has to be liberated by dedicated ubiquitin hydrolases. It is certainly possible that many extant proteins with ubiquitin-like domains used to be alternative ubiquitin precursors but have lost their cleavability. The second observation will be discussed in more detail in Sections 12.5.1 and 12.5.2. 

Sakamoto, T., Tanaka, T., Ito, Y., et al. (1999) An NMR analysis of ubiquitin recognition by yeast ubiquitin hydrolase evidence for novel substrate recognitionby a cysteine protease. Biochemistry 38, 11,634-11,642. 

Rajesh, S., Sakamoto, T., Iwamoto-Sugai, M., Shibata, T., Kohno, T., and Ito, Y. (1999) Ubiquitin binding interface mapping on yeast ubiquitin hydrolase by NMR chemical shift perturbation. Biochemistry 38, 9242-9253. 

Fig. C11.5 Three examples of knots in proteins, including the very complex knot 5i in a protein called human ubiquitin hydrolase (the rightmost image). In each case, a simple model of sticks shows the same knot as in the protein. To help the eye, each chain is colored in rainbow colors from one end to the other. The figure is reproduced, with kind permission by the authors, from the paper P. Virnau, L. Mirny and M. Kardar, Intricate Knots in Proteins Function and Evolution, PLoS Computational Biology, v. 2, pp. 1074-1079, 2006.

ZnFUBP Ubiquitin carboxyl-terminal hydrolase-like zinc finger E(MFP) 4(4) 4(4) ... 

Pickaet, C. M. and Rose, 1. A. Ubiquitin carboxyl-terminal hydrolase acts on ubiquitin carboxyl-terminal amides, J Biol Chem, 1985, 260, 7903-10. 

Larsen, C. N., Krantz, B. A., and Wilkinson, K. D. Substrate specificity of deubiquitinating enzymes ubiquitin C-terminal hydrolases. Biochemistry, 1998, 37, 3358-68. 

Structural basis for the specificity of ubiquitin C-terminal hydrolases, Embo J, 1999, 18, 3877-87. 

Eytan, E., Armon, T., Heller, H., Beck, S., and Hershko, A. Ubiquitin C-terminal hydrolase activity associated with the 26 S protease complex, J Biol Chem, 1993, 268, 4668-74. 

K. D. Ubiquitin carboxyl-terminal hydrolase (PGP 9.5) is selectively present in ubiquitinated inclusion bodies characteristic of human neurodegenerative diseases, J Pathol, 1990, 363, 153-60. 

Ubiquitinated H2A and H2B disappear at metaphase and reappear in anaphase [251-253]. Histone ubiquitination may also be involved in cell cycle progression through S phase [254]. In dividing and non-dividing cells, the ubiquitin moiety of the ubiquitinated histones is in rapid equilibrium with a pool of free ubiquitin [238,239]. The turnover of the ubiquitinated histones is presumably catalyzed by ubiquitin-C-terminal hydrolases. Uni- and multi-cellular eukaryotes contain... 

---