Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.25.1 (proteasome)
 28,817 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Testis injury models can be useful for determining the in vivo function of genes. In this study, ubiquitin, a tag for 26S-proteasome degradation, was mutated at lysine 48 (K48R) to inhibit ubiquitin chain assembly. K48R transgenic mice had testes with delayed germ cell loss following the acute injury of experimental cryptorchidism, and were resistant to the chronic injury of aging-associated testicular atrophy. After 4 days of cryptorchid-mediated heat stress, the average weight of cryptorchid testes in wild-type ubiquitin mice was significantly lower (P < 0.05) than in K48R mutant ubiquitin mice, indicating that altered ubiquitination delayed germ cell death. Light microscopy confirmed that the testicular injury, in both wild-type and K48R ubiquitin mice, was due to germ cell death. In addition, wild-type ubiquitin mice aged 19 to 22 months showed greater testicular atrophy and decreased average seminiferous tubule diameter when compared with K48R-aged testes. These results demonstrate a resistance to testicular injury conferred by the K48R mutation, suggesting that ubiquitin-mediated protein degradation is involved in the processing or modulation of testicular insults.
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PMID:Expression of a K48R mutant ubiquitin protects mouse testis from cryptorchid injury and aging. 1463 31

The experimentally induced cryptorchid mouse model is useful for elucidating the in vivo molecular mechanism of germ cell apoptosis. Apoptosis, in general, is thought to be partly regulated by the ubiquitin-proteasome system. Here, we analyzed the function of two closely related members of the ubiquitin C-terminal hydrolase (UCH) family in testicular germ cell apoptosis experimentally induced by cryptorchidism. The two enzymes, UCH-L1 and UCH-L3, deubiquitinate ubiquitin-protein conjugates and control the cellular balance of ubiquitin. The testes of gracile axonal dystrophy (gad) mice, which lack UCH-L1, were resistant to cryptorchid stress-related injury and had reduced ubiquitin levels. The level of both anti-apoptotic (Bcl-2 family and XIAP) and prosurvival (pCREB and BDNF) proteins was significantly higher in gad mice after cryptorchid stress. In contrast, Uchl3 knockout mice showed profound testicular atrophy and apoptotic germ cell loss after cryptorchid injury. Ubiquitin level was not significantly different between wild-type and Uchl3 knockout mice, whereas the levels of Nedd8 and the apoptotic proteins p53, Bax, and caspase3 were elevated in Uchl3 knockout mice. 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.
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PMID:Two closely related ubiquitin C-terminal hydrolase isozymes function as reciprocal modulators of germ cell apoptosis in cryptorchid testis. 1546