IndraLab

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"To explore the mechanisms of how reduced expression of UCHL1 promotes cell proliferation, reduces apoptosis and confers cisplatin resistance, we performed a microarray analysis to identify different genes regulated by UCHL1-knockdown."

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"Using 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay, Western blot, Hoechst 33258 staining assay and flow cytometry, we found that over-expression of UCH-L1 in MCF7 cells induced apoptosis."

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"The results indicated that the process of apoptosis triggered by UCH-L1 is, at least in part, probably through Phosphoinositide 3-kinase (PI3K) / Akt signal pathway."

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"This observation is consistent with a recent report that the over-expression of UCH-L1 induces testicular germ cell apoptosis in UCH-L1 transgenic mice."

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"UCHL1 deletion in ACTN4 -associated FSGS reduced albuminuria, glomerulosclerosis, FP effacement, GBM thickening, glomerular and tubular cell apoptosis, and ameliorated the overall renal pathology."

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"These results suggest that UCHL1 is mediator of apoptosis and targeting UCHL1 might be of great potential to overcome cisplatin resistance in ovarian cancer."

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"Loss of UCHL1, a deubiquitating enzyme responsible for regenerating monoubiquitin from the ubiquitin protein complex, decreased the rate of apoptosis in the first round of spermatogenesis and increased the numbers of premeiotic germ cells in immature mice [XREF_BIBR], whereas asymmetric distribution of UCHL1 in spermatogonia is associated with maintenance and differentiation of spermatogonial stem cells [XREF_BIBR]."

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"Thus our results: increased levels of UCHL-1, p53, BAX and cleaved caspase-3 clearly showing UCHL-1 mediated apoptosis in the cerebral cortex of WNIN/Ob rats leading to neuronal cell death."

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"3.2 Reduced expression of UCHL1 in A2780 and IGROV1 reduced cell apoptosis but increases cell proliferation."

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"Additionally, UCHL1 has been reported to inhibit cell proliferation, induce apoptosis, and stabilize p53 to slow the development of cancer cells [48]."

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"In some tumor cells, a high expression level of UCHL1 accelerates apoptosis ( Wang et al., 2008 ), countering the function of DJ-1."

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"Hence, together the results obtained in two different obese rat models strongly suggests that altered UPS leads to neuronal cell death probably in two independent ways: (i) UCHL-1 mediated apoptosis t[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

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"Jin et al. disclosed that the inhibition of UCHL1 promoted cell proliferation by increasing cells in S-phase and that the knockdown of UCHL1 reduced cell apoptosis and contributed to cisplatin resistance [63]."

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"Downregulation of UCH-L1 expression and activity in beta cells induces ER stress and apoptosis [XREF_BIBR]."

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"Uchl1 (-/-) mice had increased ER stress and beta cell apoptosis."

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"In breast cancer, ectopic expression of UCHL1 is able to induce apoptosis by stabilizing p53."

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"Yet in our study, no significant alteration of p53 was found, suggesting UCHL1 mediated apoptosis in other ways rather than by regulating p53."

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"In summary, the present data provide evidence for the first time that UCH-L1 induces apoptosis in cultured breast cancer cells in vitro and the apoptotic effect is possibly through the PI3K and Akt pathway."

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"Further studies are needed to elucidate the mechanism of UCH-L1 induced apoptosis in detail."

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"These chalcone derivatives effectively inhibit the activity of DUB, such as USP5, UCH-L3, USP2, UCH-L1, and USP8, leading to irreversible cell cycle arrest in breast, ovarian, and cervical cancer cells (IC50 = 1.5-12.5 µM), as well as inhibiting their proliferation and initiating apoptosis."

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"As shown in Fig. 3E , flow cytometry analysis revealed that knockdown of UCHL1 in MG63 cells significantly induced cell apoptosis by 25.5% compared with corresponding scramble shRNA (NC), while over-e[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

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"Moreover, three apoptotic regulation factors Bcl-2, Bax and caspase3 were evaluated by western blot which showed that the proteins promoting apoptosis (Bax and caspase3) were up-regulated and the prot[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

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"Loss of UCH-L1 decreased the rate of apoptosis in the first round of spermatogenesis and increased the numbers of premeiotic germ cells in immature mice, but spermatogenesis was partially impaired with significant reduction of spermatogonia and primary spermatocytes which mainly go to apoptosis in adult mice."

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"In mice, transgenic over-expression of UCH-L1 in spermatogonia causes a block during spermatogenesis at an early stage (pachytene) of meiosis and increased apoptosis of primary spermatocytes."

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"On the other hand, over-expression of UCHL1 in lower-UCHL1-expression Saos2 cells dramatically induced cell proliferation and suppressed cell apoptosis."

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"However, over-expression of the UCH-L1 also induces germ cell apoptosis and inhibits spermatogenesis, leading to male sterility [XREF_BIBR]."

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"UCHL1 can induce apoptosis of tumor cells and is involved in various cancers XREF_BIBR - XREF_BIBR."

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"UCHL1 enhanced cell survival by reducing apoptosis."

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"In both reproductive organs and nervous tissue, UCH-L1 promotes apoptosis."

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"UCHL1 can prevent autophagy (autophagic cell death) and promote cell proliferation by inhibiting apoptosis [40]."

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"In vitro, the downregulation of UCHL1 (UCHL1 KD) in goat SSCs increased the expression levels of apoptosis and inflammatory factors and inhibited the self-renewal and proliferation of SSCs."

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"UCH-L1 also blocks the proliferation and induces apoptosis in breast cancer cells (26,80)."

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"In addition, UCHL1 overexpression enhanced cell viability and promoted oxidative damage, apoptosis and senescence in H 2 O 2 -induced HEI-OC1 cells."

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"UCH-L1 also induced apoptosis in breast cancer cells via the PI3K/Akt signaling pathway (80)."

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"To this end, we investigated whether UCHL1 regulated proinflammatory cytokines induced MSC apoptosis."

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"Taken together, these findings indicated that UCHL1, negatively regulated by Sp1, promoted H O -mediated cell injury, oxidative stress, apoptosis and senescence, and modulated NF-κB signaling in HEI-OC1 cells."

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"Similarly, H O -induced HEI-OC1 cell apoptosis was also restored by UCHL1 overexpression."

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"This effect of UCHL1 on NF-κB signaling was abrogated by Sp1 overexpression.In conclusion, the present study suggested that UCHL1, negatively regulated by Sp1, could promote H O -mediated cell injury, oxidative stress, apoptosis and senescence and inhibit NF-κB signaling in an in vitro model of ARHL."

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"When UCH-L1 expression is restored, UCH-L1 regulates key cyclin levels (such as p53), inhibits proliferation and promotes apoptosis of cancer cells (25,26)."

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"Because overexpression of the UCH-L1 transgene also inhibited spermatogenesis and induced germ cell apoptosis, leading to male sterility [19] , together with our results, we propose that proper quanti[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

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"UCHL1 in the testis can induce germ cell apoptosis and control factors that protect against apoptosis during spermatogenesis [41]."

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"These data suggest that UCHL1 inhibition suppresses MSC apoptosis induced by proinflammatory cytokines via upregulation of Bcl-2."

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"UCHL1 induced G0/G1cell cycle arrest and apoptosis of breast tumor cells."

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"These results suggest that UCHL1 mediates mitophagy and apoptosis regulated by hypoxia in chondrocytes."

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"Overexpression of UCHL1 has been found to induce apoptosis in MCF-7 cells XREF_BIBR."

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"By analyzing these neurons in gad mice, we found that a lack of UCH-L1 protects cells from acute stress-induced apoptosis ( Harada et al., 2004 )."

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"Overexpression of UCHL1 genes promoted apoptosis in cells treated with VER+ADM."

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"Upregulation of UCHL1 enhanced the reversal effect of VER on chemo-resistance to ADM and promoted cell apoptosis."

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"For instance, Ubiquitin carboxyl-terminal hydrolase L1 (UCHL1), located on chromosome 4p14, can induce apoptosis through the intrinsic, caspase dependent pathway XREF_BIBR."

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"Our results showed that UCHL1 upregulation by VER enhanced the reversal effect of VER on chemo-resistance of HCC and promoted cell apoptosis."

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"Further, UCHL1 was shown to initiate apoptosis in breast cancer through p53 stabilization [ 21 , 27 ]; in line with this we detected elevated p53 levels in the diabetic rats at protein level but not a[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

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"We hypothesize the involvement of UCHL1 mediated apoptosis in the diabetic rat muscle that needs additional experimental support.Although it has a limited secretory function, skeletal muscle is of sig[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

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"UCHL1 has been observed to be epigenetically regulated in other cancers, and is believed to induce G0/G1 cell cycle arrest and apoptosis by stabilization of p53."

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"Further analysis of the embryonic MSCs revealed that: 1) proinflammatory cytokines and related genes TNF , TNFSF13B , TNFRSF12A , TNFAIP6 , and C1QTNF6 are significantly involved in the MSC-induced immune responses in cavernous hemangiomas; 2) UCHL1 is up-regulated in the embryonic MSC apoptosis induced by proinflammatory cytokines; 3) the UCHL1-induced apoptosis of MSCs may play an important role in the MSC-induced immune responses in cavernous hemangiomas; and 4) UCHL1 can be used as a marker gene to detect embryonic MSCs at different apoptosis stages."

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"Our findings initiated future research for the rediscovery of MSCs, cancers/tumours and the UCHL1-induced apoptosis."

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"UCH-L1 downregulation enhances ER stress induced beta-cell apoptosis, and UCH-L1 deficiency was observed in beta-cells of individuals with T2DM."

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"Studies showed that UCHL1 could induce apoptosis by stabilizing p53 in breast and hepatocellular carcinoma XREF_BIBR, XREF_BIBR, and promote ovarian cancer cell apoptosis associated with Bcl-2 family proteins regulated caspase activation 37."

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"The results suggest that the proinflammatory cytokines upregulate UCHL1, which in turn promotes MSC apoptosis via Bcl-2-regulated activation of caspase 3."

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"Interestingly, Drosophila genetic studies have shown that increased UCH-L1 levels in the eye imaginal discs induces caspase dependent apoptosis, resulting in a rough eye phenotype [XREF_BIBR]."

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"UCHL1 also induced G0/G1 cell-cycle arrest and apoptosis of breast tumour cells, an activity that requires its catalytic activity and depends on the accumulation of p53 [XREF_BIBR]."

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"This downregulation of UCH-L1 promotes apoptosis due to UPS impairment [215]."

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"Ectopic UCHL1 expression in breast tumor cells suppresses cell growth and induces G0/G1 arrest and apoptosis through p53 signaling due to its DUB activity [39]."

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"To clarify the mechanism underling our observations in MCF7 and MCF7 and Adr cells, the expression of Akt and phospho-IkappaB-alpha was further investigated and results demonstrated that UCH-L1 induced apoptosis in breast cancer cells, possibly through the PI3K and Akt pathway."

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"To obtain clues to the mechanism by which elevated expression of UCH-L1 induces apoptosis in MCF7 cells, lysates from UCH-L1 over-expressing MCF7 cells and negative controls were prepared and Western blot was carried out."

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"We showed that knockdown of UCHL1 in ovarian cancer cells promoted cell proliferation by inducing S phase cell cycle and reduced apoptosis."

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"Contradictorily, UCHL1 has recently been shown to induce G0/G1 cell cycle arrest and apoptosis by stabilizing p53 and has also been shown to be frequently silenced in primary breast tumors, but not in[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

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"A previous study showed that UCHL1 overexpression supported apoptosis in verapamil- and Adriamycin-treated hepatoma cell lines (BEL-7402 and SMMC-7721) [76]."

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"Knockdown of UCHL1 by siRNA attenuated the cell apoptosis effect of combined drugs, which indicated the important role of UCHL1 in the verapamil-mediated reversal of drug resistance [76]."

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"Conversely, in hepatocellular carcinoma it was found that overexpression of UCHL1 combated chemoresistance to verapamil and adriamycin and enhanced apoptosis rates (Yang et al., 2018)."

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"Downregulation of UCH-L1 expression and activity in beta-cells induces ER stress and apoptosis."

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"These data suggest that overexpression of UCH-L1 affects spermatogenesis during meiosis and, in particular, induces apoptosis in primary spermatocytes."

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"Similarly, UCHL1 influences caspase-dependent pathways and promotes apoptosis."