Disease relevance of Uchl3

• A murine Uchl3 deletion mutant displays retinal degeneration, muscular degeneration, and mild growth retardation [1].

High impact information on Uchl3

• We identify Ub C-terminal hydrolase L1 (UCH-L1) and DEN1/NEDP1/SENP8, in addition to UCH-L3, as proteases with specificity for Nedd8 [2].
• The deletion includes Uchl3, Lmo7 and an additional 500 kb downstream of the 3' end of Lmo7 where no genes are thought to reside [3].
• We suggest that the increase in severity may reflect an interaction between Uchl3 and Lmo7 in the ubiquitin-mediated protein degradation pathway [3].
• We predicted that the region contains a single cluster of four genes that encode a TBC domain-containing protein (KIAA0603), a novel protein AK000009, the ubiquitin C-terminal hydrolase L3 (UCHL3) and an F-box/PDZ/LIM domain protein LMO7 [3].
• In contrast to the UCH L3 isozyme that is universally expressed in all tissues, UCH L1 is expressed exclusively in neurons and testis/ovary [4].

Biological context of Uchl3

• An engineered 800 kilobase deletion of Uchl3 and Lmo7 on mouse chromosome 14 causes defects in viability, postnatal growth and degeneration of muscle and retina [3].
• Examination of hippocampal long-term potentiation (LTP), a form of synaptic plasticity thought to underlie memory storage, revealed no significant differences in LTP in hippocampal slices from Uchl3-/- mice [5].
• Photoreceptor cell apoptosis in the retinal degeneration of Uchl3-deficient mice [1].

Anatomical context of Uchl3

• In contrast, Uchl3 knockout mice showed profound testicular atrophy and apoptotic germ cell loss after cryptorchid injury [6].
• In conclusion, the response of gad and Uchl3 knockout mice to androgen withdrawal suggests a reciprocal function of the two UCH enzymes in the caput epididymis [7].
• Using immunocytochemistry, UCH-L1 was selectively detected on the plasma membrane, whereas UCH-L3 was mainly detected in the cytoplasm, suggesting that these isozymes have distinct functions in mouse eggs [8].
• Western blot analysis detected UCH-L1 in spermatogonia and Sertoli cells, whereas UCH-L3 was detected in spermatocytes and spermatids [9].
• In the normal retina, UCH-L3 was enriched in the photoreceptor inner segment that contains abundant mitochondria [1].

Other interactions of Uchl3

• These results demonstrate that UCH-L1 and UCH-L3 function differentially to regulate the cellular levels of anti-apoptotic, prosurvival, and apoptotic proteins during testicular germ cell apoptosis [6].
• Hence, loss of UCH-L3 leads to mitochondrial oxidative stress-related photoreceptor cell apoptosis in a caspase-independent manner [1].

Analytical, diagnostic and therapeutic context of Uchl3

• The caput epididymides of gad mice were resistant to apoptotic stress induced by efferent duct ligation, whereas Uchl3 knockout mice showed a marked increase in apoptotic cells following ligation [7].

References