The Region-Specific Functions of Two Ubiquitin C-Terminal Hydrolase Isozymes along the Epididymis

Kwon, Jungkee; Sekiguchi, Satoshi; Wang, Yu-Lai; Setsuie, Rieko; Yoshikawa, Yasuhiro; Wada, Keiji

doi:10.1538/expanim.55.35

Cited by 14 publications

(12 citation statements)

References 38 publications

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“…In gad mice, the levels of the antiapoptotic proteins Bcl-2/Bcl-xL were significantly elevated in the caput epididymidis regardless of efferent duct ligation. These results demonstrate that the two UCH isozymes, UCHL1 and UCHL3, have distinct expression levels along the epididymis and apparent reciprocal functions in response to apoptotic stress [20], as was shown with cryptorchid stress [19].…”

Section: Uch-l1 and Uch-l3 Have Region-specific Expression Along The supporting

confidence: 69%

The New Function of Two Ubiquitin C-Terminal Hydrolase Isozymes as Reciprocal Modulators of Germ Cell Apoptosis

Kwon

2007

Exp. Anim.

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Section: Uch-l1 and Uch-l3 Have Region-specific Expression Along The supporting

confidence: 69%

The New Function of Two Ubiquitin C-Terminal Hydrolase Isozymes as Reciprocal Modulators of Germ Cell Apoptosis

Kwon

2007

Exp. Anim.

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“…Therefore, it is conceivable that UCH-L1 and UCH-L3 have different functional roles in oocytes and embryos, as was shown in the testis/ epididymis. 9,11 Although our studies show that UCH-L3 is highly expressed in the cytoplasm of oocytes and embryos, we found no difference in the fertilization rate and litter size in Uchl3 knockout female mice compared with wild-type (C57BL/6J) female mice (data not shown). Thus, UCH-L3 may not impact these developmentally related processes; further research is necessary to elucidate the cytoplasmic function of this UCH.…”

Section: Discussionmentioning

confidence: 56%

“…[43][44][45] Our previous studies suggested that UCH-L1 and UCH-L3, despite their high sequence homology, 12 have distinct expression patterns and differential function in testis and epididymis. 9,11 Here we show that these two proteins have distinct distributions: UCH-L1 is exclusively expressed on the plasma membrane of oocytes and embryos, whereas UCH-L3 is diffusely expressed in the cytoplasm (Figures 1B and 2B). Therefore, it is conceivable that UCH-L1 and UCH-L3 have different functional roles in oocytes and embryos, as was shown in the testis/ epididymis.…”

Section: Discussionmentioning

confidence: 71%

Localization of Ubiquitin C-Terminal Hydrolase L1 in Mouse Ova and Its Function in the Plasma Membrane to Block Polyspermy

Sekiguchi

Kwon

Yoshida

et al. 2006

The American Journal of Pathology

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Protein degradation is essential for oogenesis and embryogenesis. The ubiquitin-proteasome system regulates many cellular processes via the rapid degradation of specific proteins. Ubiquitin carboxylterminal hydrolase L1 (UCH-L1) is exclusively expressed in neurons , testis , ovary , and placenta , each of which has unique biological activities. However , the functional role of UCH-L1 in mouse oocytes remains unknown. Here , we report the expression pattern of UCH-L1 and its isozyme UCH-L3 in mouse ovaries and embryos. 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. To further investigate the functional role of UCH-L1 in mouse eggs, we analyzed the fertilization rate of UCH-L1-deficient ova of gad female mice. Female gad mice had a significantly increased rate of polyspermy in in vitro fertilization assays, although the rate of fertilization did not differ significantly from wild-type mice. In addition, the litter size of gad female mice was significantly reduced compared with wild-type mice. These results may identify UCH-L1 as a candidate for a sperm-oocyte interactive binding or fusion protein on the plasma membrane that functions during the block to polyspermy in mouse oocytes.

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“…We report here an additional modification that may significantly have an impact on its enzymatic and/or binding activities: UCH-L1 is farnesylated and associated with neuronal membranes, including the endoplasmic reticulum. This modification is not present in UCH-L3, which appears to serve different biochemical and biological roles than UCH-L1 (22)(23)(24)(25)(26)(27)(28)(29). The amount of membrane-associated UCH-L1 (UCH-L1 M ) is linked to intracellular ␣-synuclein levels and neurotoxicity.…”

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confidence: 99%

Membrane-associated farnesylated UCH-L1 promotes α-synuclein neurotoxicity and is a therapeutic target for Parkinson's disease

Liu

Meray

Grammatopoulos³

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

126

131

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Ubiquitin C-terminal hydrolase-L1 (UCH-L1) is linked to Parkinson's disease (PD) and memory and is selectively expressed in neurons at high levels. Its expression pattern suggests a function distinct from that of its widely expressed homolog UCH-L3. We report here that, in contrast to UCH-L3, UCH-L1 exists in a membrane-associated form (UCH-L1 M ) in addition to the commonly studied soluble form. C-terminal farnesylation promotes the association of UCH-L1 with cellular membranes, including the endoplasmic reticulum. The amount of UCH-L1 M in transfected cells is shown to correlate with the intracellular level of ␣-synuclein, a protein whose accumulation is associated with neurotoxicity and the development of PD. Reduction of UCH-L1 M in cell culture models of ␣-synuclein toxicity by treatment with a farnesyltransferase inhibitor (FTI-277) reduces ␣-synuclein levels and increases cell viability. Proteasome function is not affected by UCH-L1 M , suggesting that it may negatively regulate the lysosomal degradation of ␣-synuclein. Therefore, inhibition of UCH-L1 farnesylation may be a therapeutic strategy for slowing the progression of PD and related synucleinopathies.farnesylation ͉ synuclein

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The Region-Specific Functions of Two Ubiquitin C-Terminal Hydrolase Isozymes along the Epididymis

Abstract: We previously showed that gad mice, which are deficient for ubiquitin C-terminal hydrolase L1 (UCH-L1

Cited by 14 publications

References 38 publications

The New Function of Two Ubiquitin C-Terminal Hydrolase Isozymes as Reciprocal Modulators of Germ Cell Apoptosis

The New Function of Two Ubiquitin C-Terminal Hydrolase Isozymes as Reciprocal Modulators of Germ Cell Apoptosis

Localization of Ubiquitin C-Terminal Hydrolase L1 in Mouse Ova and Its Function in the Plasma Membrane to Block Polyspermy

Membrane-associated farnesylated UCH-L1 promotes α-synuclein neurotoxicity and is a therapeutic target for Parkinson's disease

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