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51.
p63, known to play a role in development, has more recently also been implicated in cancer progression. Mutations in p63 have been shown to be responsible for several human developmental diseases. Differential splicing of the p63 gene gives rise to p63 isoforms, which can act either as tumor suppressors or as oncogene. In this report, we studied the effects of naturally occurring TAp637 mutants on the regulation of p53/p63 and p63 specific target genes. We observed significant differences among p63 mutants to regulate the p53/p63 and p63 specific target genes. Additionally, we observed a differential effect of p63 mutants on wildtype-p63-mediated induction ofp53/p63 and p63 specific target genes. We also demonstrated that these mutants differentially regulate the binding of wildtype p63 to the promoter of target genes. Furthermore, the effects of these mutants on cell death and survival were consistent with their ability to regulate the downstream targets when compared to wildtype TAp63T. In summary, our data demonstrate that p63 mutants exhibit differential effects on p63 and p53/p63 specific target genes and on the induction of apoptosis, and provide further insight into the function of p63. 相似文献
52.
We have previously characterized the biogenesis of the human CD8α protein expressed in rat epithelial cells. We now describe the biosynthesis, post-translational maturation and hetero-oligomeric assembly of the human CD8α/p56lck protein complex in stable transfectants obtained from the same cell line. There were no differences in the myristilation of p56lck, or in the dimerization, O-glycosylation and transport to the plasma membrane of CD8α, between cells expressing either one or both proteins. In the doubly expressing cells, dimeric forms of CD8α established hetero-oligomeric complexes with p56lck, as revealed by co-immunoprecipitation assays performed with anti-CD8α antibody. Moreover, p56lck bound in these hetero-oligomeric complexes was endowed with auto- and hetero-phosphorylating activity. The present study shows that: (1) the newly synthesized p56lck binds rapidly to CD8α and most of the p56lck is bound to CD8α at steady state; (2) CD8α/p56lck protein complexes are formed at internal membranes as well as at the plasma membrane; and (3) about 50% of complexed p56lck reaches the cell surface. 相似文献
53.
microRNAs (miRNAs) have been revealed to participate in the pathological process of atherosclerosis (AS). However, the exact role of miR-338-3p, a target miRNA of BMP and activin membrane-bound inhibitor (BAMBI), and its possible molecular mechanism in AS remain unidentified. In this study, we found that BAMBI was significantly decreased, whereas miR-338-3p increased in patients with AS and oxidized low-density lipoprotein (ox-LDL)-induced HUVEC cells. Furthermore, overexpression of miR-338-3p significantly decreased cell viability and elevated cell apoptosis, whereas its inhibition significantly promoted cell viability and inhibited cell apoptosis in ox-LDL-induced HUVEC cells. Moreover, miR-338-3p overexpression increased TGF-β/Smad pathway activation in ox-LDL-induced HUVEC cells. A dual-luciferase reporter assay confirmed the direct interaction between miR-338-3p and the 3′-untranslated region of BAMBI messenger RNA. Furthermore, the suppression of BAMBI ameliorated the effect of miR-338-3p inhibition against ox-LDL-induced HUVEC cell injury. In conclusion, our study thus suggests that miR-338-3p promoted ox-LDL-induced HUVEC cell injury by targeting BAMBI and activating the TGF-β/Smad pathway, which may provide a novel and promising therapeutic target for AS. 相似文献
54.
Lipocalin 2 (LCN2) is produced by mammalian hosts to bind bacterial siderophore and sequester free iron as part of an innate immune response, and could also play a role in tissue iron homeostasis, but thus far, little is known about its expression in the CNS. The present study was carried out to study the expression of the lipocalin in the normal rat brain and after neuronal injury induced by kainate (KA). Low levels of LCN2 mRNA and protein expression were detected in most regions of the normal brain except the olfactory bulb, brainstem and cerebellum. KA lesions resulted in damage to the hippocampus, leading to an early increase at three days and a sustained elevation in LCN2 mRNA level of 16-fold, and protein expression at 80-fold in the lesioned tissue compared to controls at 2 weeks post-KA injection. The sustained elevation in mRNA expression was not detected among other lipocalins surveyed using real-time RT-PCR - apoD, PGDS, Rbp4 and LCN5. Single and double immunostaining confirmed that LCN2 is present in astrocytes in the olfactory bulb, brainstem and cerebellum of the normal brain, and reactive astrocytes in the KA-lesioned hippocampus. In conclusion, the present study showed LCN2 to be present in select brain regions, and is upregulated in astrocytes after neuronal injury induced by kainate. We postulate that, as in the periphery, LCN2 may have a role in iron transport or trafficking in the CNS. 相似文献
55.
Apoptosis and cell recovery in response to oxidative stress in p53-deficient prostate carcinoma cells 总被引:3,自引:0,他引:3
We have studied the effects of different concentrations of H(2)O(2) on the proliferation of PC-3 prostate carcinoma cells. Since this cell line lacks functional p53, we sought to characterize whether apoptotic response to the oxidative insult was altered such that, unlike in cells containing functional p53 apoptosis may be reduced and replaced by other mechanisms of cellular arrest and death. We did not observe necrosis in PC-3 cells treated with H(2)O(2) concentrations of up to 500 microM. In the presence of 50 microM H(2)O(2), arrest was observed in the G2-phase of the cell cycle, along with p53-independent apoptosis. In the presence of 500 microM H(2)O(2), addition of l-buthionine sulfoximine increased the percentage of apoptotic cell death. Senescence-associated cell arrest was never observed. Moreover, some of the treated cells seemed to be resistant to oxidative damage. These cells re-entered the cell cycle and proliferated normally. Analysis of the expression of p21(waf1) and of p21 protein levels, as well as the activity of caspase-3 and caspase-8, allowed us to characterize some aspects of the arrest of PC-3 cells in G2 and the apoptotic response to oxidative stress in the absence of functional p53. 相似文献
56.
M E Fiori C Barbini T L Haas N Marroncelli M Patrizii M Biffoni R De Maria 《Cell death and differentiation》2014,21(5):774-782
Lung cancer is the leading cause of tumor-related death. The lack of effective treatments urges the development of new therapeutic approaches able to selectively kill cancer cells. The connection between aberrant microRNA (miRNA – miR) expression and tumor progression suggests a new strategy to fight cancer by interfering with miRNA function. In this regard, LNAs (locked nucleic acids) have proven to be very promising candidates for miRNA neutralization. Here, we employed an LNA-based anti-miR library in a functional screening to identify putative oncogenic miRNAs in non-small-cell lung cancer (NSCLC). By screening NIH-H460 and A549 cells, miR-197 was identified as a new functional oncomiR, whose downregulation induces p53-dependent lung cancer cell apoptosis and impairs the capacity to establish tumor xenografts in immunodeficient mice. We further identified the two BH3-only proteins NOXA and BMF as new miR-197 targets responsible for induction of apoptosis in p53 wild-type cells, delineating miR-197 as a key survival factor in NSCLC. Thus, we propose the inhibition of miR-197 as a novel therapeutic approach against lung cancer. 相似文献
57.
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59.
Ying Wang Yunjing Zhang Xinwan Su Qiongzi Qiu Yuan Yuan Chunhua Weng Sailan Zou Yan Tian Weidong Han Pengyuan Liu Xingyi Guo Jianhua Mao Xianghui Fu Ping Wang Weiqiang Lin 《International journal of biological sciences》2022,18(4):1491
Clear cell renal cell carcinoma (ccRCC) is a primary kidney cancer with high aggressive phenotype and extremely poor prognosis. Accumulating evidence suggests that circular RNAs (circRNAs) play pivotal roles in the occurrence and development of various human cancers. However, the expression, clinical significance and regulatory role of circRNAs in ccRCC remain largely unclear. Here we report that circDVL1 to be reduced in the serums and tissues from ccRCC patients, and to negatively correlate with ccRCC malignant features. Overexpression of circDVL1 inhibits proliferation, induces G1/S arrest, triggers apoptosis, and reduces migration and invasion in different ccRCC cells in vitro. Correspondingly, circDVL1 overexpression suppresses ccRCC tumorigenicity in a mouse xenograft model. Mechanistically, circDVL1 serves as a sponge for oncogenic miR-412-3p, thereby preventing miR-412-3p-mediated repression of its target protocadherin 7 (PCDH7) in ccRCC cells. Collectively, our results demonstrate that circDVL1 exerts tumor-suppressive function during ccRCC progression through circDVL1/miR-412-3p/PCDH7 axis, and suggest that circDVL1 could be a novel diagnostic and prognositc marker and therapeutic target for ccRCC. 相似文献
60.