Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0162473 (Frey)
 2,599 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In vivo, ubiquitin exists both free and conjugated through its carboxyl terminus to the alpha- and epsilon-amino groups of a wide variety of cellular proteins. Ubiquitin carboxyl-terminal hydrolytic activity is likely a necessary step in the regeneration of the ubiquitin cofactor from ubiquitin-protein conjugates. In addition, this type of activity is required to generate the active, monomeric ubiquitin from the only known gene products: the polyprotein precursor and various ubiquitin fusion proteins. Thus, this activity is of vital importance to systems that utilize ubiquitin as a cofactor. A generic substrate, ubiquitin ethyl ester, was previously developed [Wilkinson, K. D., Cox, M. J., Mayer, A. N., & Frey, T. (1986) Biochemistry 25, 6644-6649] and utilized here to monitor the fractionation of these activities from calf thymus. By use of a rapid HPLC assay, four distinct, ubiquitin-specific esterases were identified and separated. A previously undescribed activity has been resolved and characterized, in addition to the bovine homologue of ubiquitin carboxyl-terminal hydrolase purified from rabbit reticulocytes. Two other activities resemble deconjugating activities previously detected in crude extracts but not previously purified. These activities appear to form a family of mechanistically related hydrolases. All four activities are inhibited by iodoacetamide, indicating the presence of an essential thiol group, and are inhibited to various extents by manganese. All have specific ubiquitin binding sites as judged by the low observed Km values (0.6-30 microM). The carboxyl-terminal aldehyde of ubiquitin is a potent inhibitor of these enzyme activities, with Ki values approximately 1000-fold lower than the respective Km values.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Detection, resolution, and nomenclature of multiple ubiquitin carboxyl-terminal esterases from bovine calf thymus. 253 53

The present study examined alterations of spinal ubiquitin C-terminal hydrolase L1 (UCHL1), ubiquitin expression and glial activation in the cancer-induced bone pain rats. Furthermore, whether inhibition of spinal UCHL1 could alleviate cancer-induced bone pain was observed. The CIBP model was established by intrathecal Walker 256 mammary gland carcinoma cells in SD rats. The rats of CIBP developed significant pain facilitation in the Von Frey test. Double immunofluorescence analyses revealed that in the spines of CIBP rats, ubiquitin co-localized with NeuN, Iba-1 or GFAP; UCHL1 and NeuN were co-expressed and UCHL1 also co-localized with ubiquitin. The CIBP model induced up-regulation of ubiquitin and UCHL1 in the spines, as well as glial activation. Inhibition of spinal UCHL1 attenuated pain facilitation by down-regulation of ubiquitin expression and glial activation. in the CIBP rats. Our data suggests that UCHL1/ubiquitin distributed and increased in the spines of CIBP rats, that glial activation also increased in the CIBP model and that inhibition of spinal UCHL1 may be an effective method to alleviate cancer-induced bone pain.
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PMID:Inhibition of spinal UCHL1 attenuates pain facilitation in a cancer-induced bone pain model by inhibiting ubiquitin and glial activation. 2750 24