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Literature summary for 3.4.19.12 extracted from

  • Gong, B.; Cao, Z.; Zheng, P.; Vitolo, O.V.; Liu, S.; Staniszewski, A.; Moolman, D.; Zhang, H.; Shelanski, M.; Arancio, O.
    Ubiquitin hydrolase Uch-L1 rescues beta-amyloid-induced decreases in synaptic function and contextual memory (2006), Cell, 126, 775-788.
    View publication on PubMed

Application

Application Comment Organism
medicine ubiquitin hydrolase Uch-L1 could be an attractive target for the development of new therapeutic approaches to Alzheimer's disease Mus musculus
medicine Uch-L1 is required for normal synaptic and cognitive function. Uch-L1 activity plays a role in normal contextual fear learning. Transduction of Uch-L1 protein fused to the transduction domain of HIV-transactivator protein restores normal enzymatic activity and synaptic function both in hippocampal slices treated with oligomeric Ab and in the APP/PS1 mouse model of Alzheimer’s disease. Intraperitoneal injections with the fusion protein improve the retention of contextual learning in APP/PS1 mice over time. Beneficial effect of the Uch-L1 fusion protein is associated with restoration of normal levels of the protein kinase A-regulatory subunit IIa, PKA activity, and cAMP response element binding protein phosphorylation Mus musculus

Cloned(Commentary)

Cloned (Comment) Organism
recombinant fusion proteins expressed in Escherichia Coli BL21(DE3)pLysS cells Mus musculus

Protein Variants

Protein Variants Comment Organism
C90S mutant of the Uch-L1 protein fused to the transduction domain of HIV-transactivator protein, has little activity Mus musculus
additional information mutant of the Uch-L1 protein fused to the transduction domain of HIV-transactivator protein with a 57 amino acid deletion (130-186) including the H161 site, is inactive Mus musculus
S18Y mutant of the Uch-L1 protein fused to the transduction domain of HIV-transactivator protein, has similar hydrolase activity than the unmutated fusion protein Mus musculus

Inhibitors

Inhibitors Comment Organism Structure
amyloid beta 30% inhibition Mus musculus
LDN-57444 reversible, competitive, active site-directed isatin oxime, 70% inhibition with 0.005 mM Mus musculus

Localization

Localization Comment Organism GeneOntology No. Textmining
soluble Uch-L1 protein fused to the transduction domain of HIV-transactivator protein exclusively present in the soluble fraction of hippocampal homogenates Mus musculus
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-

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
additional information Mus musculus ubiquitin hydrolase Uch-L1 rescues beta-amyloid-induced decreases in synaptic function and contextual memory ?
-
?

Organism

Organism UniProt Comment Textmining
Mus musculus
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C57/BL6 mice or APP/PS1 mice
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Mus musculus Q9R0P9
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-

Purification (Commentary)

Purification (Comment) Organism
fusion proteins purified by ProBond purification system Mus musculus

Source Tissue

Source Tissue Comment Organism Textmining
brain
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Mus musculus
-
hippocampus
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Mus musculus
-

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
additional information ubiquitin hydrolase Uch-L1 rescues beta-amyloid-induced decreases in synaptic function and contextual memory Mus musculus ?
-
?
ubiquitin-7-amido-4-methylcoumarin + H2O
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Mus musculus ubiquitin + 7-amino-4-methylcoumarin
-
?

Synonyms

Synonyms Comment Organism
ubiquitin C-terminal hydrolase L1
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Mus musculus
ubiquitin hydrolase Uch-L1
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Mus musculus
UCH-L1
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Mus musculus