NCBI Summary:
The protein encoded by this gene belongs to the peptidase C12 family. This enzyme is a thiol protease that hydrolyzes a peptide bond at the C-terminal glycine of ubiquitin. This gene is specifically expressed in the neurons and in cells of the diffuse neuroendocrine system. Mutations in this gene may be associated with Parkinson disease.[provided by RefSeq, Sep 2009]
General function
Enzyme, Ligase
Comment
Cellular localization
Cytoplasmic
Comment
Ovarian function
Luteinization, Oocyte maturation, Early embryo development
, Germinal vesicle breakdown
, First polar body extrusion
Comment
UCH-L1 inhibitor LDN-57444 hampers mouse oocyte maturation by regulating oxidative stress and mitochondrial function and reducing ERK1/2 expression. Pan Y et al. (2020) Oocyte maturation is a prerequisite for successful fertilization and embryo development. Incomplete oocyte maturation can result in infertility. Ubiquitin carboxy-terminal hydrolase L1 (UCH-L1) has been found to be implicated in oocyte maturation and embryo development. However, the cellular and molecular mechanisms of UCH-L1 underlying oocyte maturation have not been fully elucidated. In the present study, we observed that the introduction of UCH-L1 inhibitor LDN-57444 suppressed first polar body extrusion during mouse oocyte maturation. The inhibition of UCH-L1 by LDN-57444 led to the notable increase of reactive oxygen species (ROS) level, conspicuous reduction of glutathione (GSH) content and mitochondrial membrane potential (MMP), and blockade of spindle body formation. As a conclusion, UCH-L1 inhibitor LDN-57444 suppressed mouse oocyte maturation by improving oxidative stress, attenuating mitochondrial function, curbing spindle body formation and down-regulating ERK1/2 expression, providing a deep insight into the cellular and molecular basis of UCH-L1 during mouse oocyte maturation.//////////////////
Essential role of ubiquitin C-terminal hydrolases UCHL1 and UCHL3 in mammalian oocyte maturation. Mtango NR et al. Ubiquitin C-terminal hydrolases (UCHs) comprise a family of deubiquitinating enzymes that play a role in the removal of multi-ubiquitin chains from proteins that are posttranslationally modified by ubiquitination to be targeted for proteolysis by the 26S proteasome. The UCH-enzymes also generate free monomeric ubiquitin from precursor multi-ubiquitin chains and, in some instances, may rescue ubiquitinated proteins from degradation. This study examined the roles of two oocyte-expressed UCHs, UCHL1 and UCHL3 in murine and rhesus monkey oocyte maturation. The Uchl1 and Uchl3 mRNAs were highly expressed in GV and MII oocytes, and were associated with the oocyte cortex (UCHL1) and meiotic spindle (UCHL3). Microinjection of the UCH-family enzyme inhibitor, ubiquitin-aldehyde (UBAL) to GV oocytes prevented oocyte meiotic progression beyond metaphase I in a majority of treated oocytes and caused spindle and first polar body anomalies. Injection of antibodies against UCHL3 disrupted oocyte maturation and caused meiotic anomalies, including abnormally long meiotic spindles. A selective, cell permeant inhibitor of UCHL3, 4, 5, 6, 7-Tetrachloroidan-1, 3-dione also caused meiotic defects and chromosome misalignment. Cortical granule localization in the oocyte cortex was disrupted by UBAL injected after oocyte maturation. We conclude that the activity of oocyte UCHs contributes to oocyte maturation by regulating the oocyte cortex and meiotic spindle. J. Cell. Physiol. ? 2011 Wiley-Liss, Inc.
PTOV1 is associated with UCH-L1 and in response to estrogen stimuli during the mouse oocyte development. Yao YW et al. To investigate the biological significance of ubiquitin carboxyl-terminal hydrolase L1 (UCH-L1) involvement in oocyte maturation, we screened for proteins that bound to UCH-L1 in mouse ovaries, and we found that the prostate tumor overexpressed-1 (PTOV1) protein was able to bind to UCH-L1. PTOV1 is highly expressed in prostate cancers and considered as a potential marker for carcinogenesis and the progress of prostate cancer. It was reported that PTOV1 plays an important role in cell cycle regulation, but its role in mammalian oocyte development and meiosis is still unclear. In this paper, it was found that the expression levels of PTOV1 in mouse ovaries progressively increased from prepubescence to adulthood. And we found by immunohistochemistry that PTOV1 spreaded in both the cytoplasm and nuclei of oocytes during prepuberty, but in normal adult mouse oocytes, it concentrated not only in nuclei but also on the plasma membrane, though in some oocytes with abnormal shapes, PTOV1 did not display the typical distribution patterns. In granulosa cells, however, it was found to locate in the cytoplasm at all the selected ages. In postnatal mouse ovaries (28?days), estradiol treatment induced the adult-specific distribution pattern of PTOV1 in oocytes. In addition, UCH-L1 was shown to be associated with CDK1, which participated in the regulation of cell cycle and oocyte maturation. Therefore, we propose that the distribution changes of PTOV1 are age-dependent, and significant for mouse oocyte development and maturation. Moreover, the discovery that PTOV1 is associated with UCH-L1 in mouse oocytes supports the explanations for that UCH-L1 is involved in oocyte development and maturation, especially under the regulation of estrogen.
Role of Ubiquitin Carboxyl-Terminal Hydrolase-L1 in Anti-Polyspermy Defense of Mammalian Oocytes. Susor A et al. The ubiquitin-proteasome system regulates many cellular processes through a rapid proteasomal degradation of ubiquitin-tagged proteins. Ubiquitin carboxyl-terminal hydrolase-L1 (UCHL1) is one of the most abundant proteins in mammalian oocytes. It has weak hydrolytic activity as a monomer and acts as an ubiquitin-ligase in its dimeric/oligomeric form. Recently published data show that insufficiency in UCHL1 activity coincides with polyspermic fertilization; however, the mechanism by which UCHL1 contributes to this process remains unclear. Using UCHL1-specific inhibitors, we induced a high rate of polyspermy in bovine zygotes after in vitro fertilization. At the same time, we detected decreased levels in the pool of monomeric ubiquitin and polyubiquitin. The presence of UCHL1 inhibitors in maturation medium enhanced the formation of presumptive UCHL1 oligomers and subsequently increased the abundance of K63-linked poly-ubiquitin chains in oocytes. We analyzed the dynamics of cortical granules (CGs) in UCHL1-inhibited oocytes; both the migration of CGs toward the cortex during oocyte maturation and the fertilization-induced extrusion of CGs were impaired. These alterations in CGs dynamics coincided with high polyspermy incidence in the in vitro produced, UCHL1-inhibited zygotes. These data indicate that the anti-polyspermy defense in bovine oocytes may rely on UCHL1 controlled functioning of cortical granules.
Proteomic analysis of porcine oocytes during in vitro maturation reveals essential role for the ubiquitin C-terminal hydrolase-L1. Susor A et al. In this study, we performed proteomic analysis of porcine oocytes during in vitro maturation. Comparison of oocytes at the initial and final stages of meiotic division characterized candidate proteins that were differentially synthesized during in vitro maturation. While the biosynthesis of many of these proteins was significantly decreased, we found four proteins with increased biosynthetic rate, which are supposed to play an essential role in meiosis. Among them, the ubiquitin C-terminal hydrolase-L1 (UCH-L1) was identified by mass spectrometry. To study the regulatory role of UCH-L1 in the process of meiosis in pig model, we used a specific inhibitor of this enzyme, marked C30, belonging to the class of isatin O-acyl oximes. When germinal vesicle (GV) stage cumulus-enclosed oocytes were treated with C30, GV breakdown was inhibited after 28 h of culture, and most of the oocytes were arrested at the first meiosis after 44 h. The block of metaphase I-anaphase transition was not completely reversible. In addition, the inhibition of UCH-L1 resulted in elevated histone H1 kinase activity, corresponding to cyclin-dependent kinase(CDK1)-cyclin B1 complex, and a low level of monoubiquitin. These results supported the hypothesis that UCH-L1 might play a role in metaphase I-anaphase transition by regulating ubiquitin-dependent proteasome mechanisms. In summary, a proteomic approach coupled with protein verification study revealed an essential role of UCH-L1 in the completion of the first meiosis and its transition to anaphase.
Expression regulated by
LH
Comment
Gene expression decreased. Luteinization of porcine preovulatory follicles leads to systematic changes in follicular gene expression. Agca C et al. The LH surge initiates the luteinization of preovulatory follicles and causes hormonal and structural changes that ultimately lead to ovulation and the formation of corpora lutea. The objective of the study was to examine gene expression in ovarian follicles (n = 11) collected from pigs (Sus scrofa domestica) approaching estrus (estrogenic preovulatory follicle; n = 6 follicles from two sows) and in ovarian follicles collected from pigs on the second day of estrus (preovulatory follicles that were luteinized but had not ovulated; n = 5 follicles from two sows). The follicular status within each follicle was confirmed by follicular fluid analyses of estradiol and progesterone ratios. Microarrays were made from expressed sequence tags that were isolated from cDNA libraries of porcine ovary. Gene expression was measured by hybridization of fluorescently labeled cDNA (preovulatory estrogenic or -luteinized) to the microarray. Microarray analyses detected 107 and 43 genes whose expression was decreased or increased (respectively) during the transition from preovulatory estrogenic to -luteinized (P<0.01). Cells within preovulatory estrogenic follicles had a gene-expression profile of proliferative and metabolically active cells that were responding to oxidative stress. Cells within preovulatory luteinized follicles had a gene-expression profile of nonproliferative and migratory cells with angiogenic properties. Approximately, 40% of the discovered genes had unknown function.
Ovarian localization
Oocyte
Comment
Maternal housekeeping proteins translated during bovine oocyte maturation and early embryo development. Massicotte L et al. Protein synthesis from maternal mRNA is needed to sustain oocyte maturation and embryo development prior to the maternal-embryonic transition (MET). Therefore, proteins that are expressed throughout this time are important and may be considered as maternal housekeeping proteins (MHKP). Our objectives were first, identify the translated protein patterns of bovine embryo development and secondly, determine the MHKP. Proteins synthesized during oocyte maturation and embryo development (2, 4 and 8-cell stages) were labeled using [S(35)]-Met and [S(35)]-Cys, and visualized by 2-DE. Embryos were cultured with alpha-amanitine to inhibit new transcription. Only 46 proteins were present throughout all stages. Ten spots were identified by MALDI-TOF and MS/MS: HSC71; HSP70; CypA; UCH-L1; GSTM5; Cct5; E-FABP; 2,3-BPGM, ubiquitin-conjugating enzyme E2D3; and beta-actin/gamma-actin. A new method called in silico protein identification confirmation was developed using EST databases. This method is a promising approach for use in rare tissue or from species with an incomplete protein database. This study has revealed that the translated protein patterns show a transition that brings the embryo to the MET. The needs in translated proteins between oocyte maturation and embryo development are different. In summary, this study represents the bases for future proteomics studies on bovine oocytes and embryos.
Follicle stages
Comment
Ubiquitin carboxyl-terminal hydrolase L1 contributes to the oocyte selective elimination in prepubertal mouse ovaries. Gu YQ et al. Apoptosis of abnormal oocytes is essential for defective oocyte elimination during prepubertal ovary development, and the ubiquitin system regulates the cell apoptosis via the degradation of specific proteins. Ubiquitin carboxyl-terminal hydrolase L1 (UCH-L1) is a component of the ubiquitin system, and the UCH-L1-dependent apoptosis is important for spermatogenesis. In the present study, the change in the number of follicles and the expression of UCH-L1 in oocytes were determined in prepubertal mouse ovaries by immunohistochemical techniques. A significant decrease in the follicular pool was found in prepubertal mouse ovaries during the period of day 21 to day 28 after birth, and accordingly, the UCH-L1 protein expression was increased, to some degree in association with Jun activation domain-binding protein 1 (Jab1) and cyclin-dependent kinase inhibitor p27(Kipl). The increased UCH-L1 protein, together with the corresponding changes of Jab1 was detected in morphologically abnormal oocytes of prepubertal ovaries. Through the immunofluorescent colocalization, UCH-L1 was shown concentrating in abnormal oocytes, and a parallel change in Jab1 was also seen. The affinity analysis confirmed the interaction between UCH-L1 and Jab1 in ovaries. These results suggest that UCH-L1 plays an important role, possibly in association with Jab1 and p27(Kipl), in selective elimination of abnormal oocytes during mouse prepubertal development.
Phenotypes
Mutations
2 mutations
Species: mouse
Mutation name: None
type: null mutation fertility: subfertile Comment: Localization of ubiquitin C-terminal hydrolase l1 in mouse ova and its function in the plasma membrane to block polyspermy. Sekiguchi S et al. Protein degradation is essential for oogenesis and embryogenesis. The ubiquitin-proteasome system regulates many cellular processes via the rapid degradation of specific proteins. Ubiquitin carboxyl-terminal 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.
Species: mouse
Mutation name: None
type: null mutation fertility: infertile - ovarian defect Comment: Effects of ubiquitin C-terminal hydrolase-L1 deficiency on mouse ova. Koyanagi S et al. Maternal proteins are rapidly degraded by the ubiquitin-proteasome system during oocyte maturation in mice. Ubiquitin C-terminal hydrolase L1 (UCH-L1) is highly and specifically expressed in mouse ova and is involved in the polyspermy block. However, the role of UCH-L1 in the underlying mechanism of polyspermy block is poorly understood. To address the issue, we performed a comprehensive proteomic analysis to identify maternal proteins which were relevant to the role of UCH-L1 in mouse ova using UCH-L1-deficient gad. Furthermore, we assessed morphological features in gad mouse ova using transmission electron microscopy. NACHT, LRR, and PYD domain-containing family (NALP) proteins and endoplasmic reticulum chaperones were identified by proteomic analysis. We also found that the 'maternal antigen that embryos require' (MATER, also known as NLRP5) protein level increased significantly in gad mouse ova compared with that in wild-type. In an ultrastructural study, gad mouse ova contained less endoplasmic reticulum in the cortex than wild-type mice. These results provide new insights into the role of UCH-L1 and the mechanism of polyspermy block in mouse ova.