Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.1.27.1 (RNase)
 16,360 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cadherins are discussed not in terms of their adhesive function but rather as morphoregulatory proteins. Changes in gene expression following cadherin transfection of cells in culture or by overexpression in embryos have, until now, not been reported. We established a protocol for stable transfection of Xenopus XTC cells and generated cells bearing high levels of membrane-integrated mouse uvomorulin (E-cadherin) or Xenopus XB-cadherin. These cell lines showed drastically impaired substrate adhesion on fibronectin and laminin. In immunoblot and radioimmunoprecipitation experiments, we found that fibronectin and alpha 3/beta 1 integrin are downregulated. The reduced amounts of proteins result from a decrease of the respective mRNAs as proven by RNase protection assays. Coprecipitations revealed that transfected cadherin molecules are complexed with alpha-catenin and beta-catenin at plasma membranes. However, the alpha-catenin present in the XB-cadherin complex differs immunologically from that found in the uvomorulin complex. When a truncated form of XB-cadherin lacking 38 of the most C-terminal amino acids was expressed in XTC cells, complex formation with endogenous catenins was abolished. In these transfectants, substrate adhesion was not affected. These results prove that complex formation of transfected cadherins in XTC cells with endogenous beta-catenin correlates with altered synthesis of certain substrate adhesion molecules.
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PMID:Cadherin transfection of Xenopus XTC cells downregulates expression of substrate adhesion molecules. 765 25

We have previously shown (K. Kas et al, Nat. Genet., 15: 170-174, 1997) that the developmentally regulated zinc finger gene pleomorphic adenoma gene 1 (PLAG1) is the target gene in 8q12 in pleomorphic adenomas of the salivary glands with t(3;8)(p21;q12) translocations. The t(3;8) results in promoter swapping between PLAG1 and the constitutively expressed gene for beta-catenin (CTNNB1), leading to activation of PLAG1 expression and reduced expression of CTNNB1. Here we have studied the expression of PLAG1 by Northern blot analysis in 47 primary benign and malignant human tumors with or without cytogenetic abnormalities of 8q12. Overexpression of PLAG1 was found in 23 tumors (49%). Thirteen of 17 pleomorphic adenomas with a normal karyotype and 5 of 10 with 12q13-15 abnormalities overexpressed PLAG1, which demonstrates that PLAG1 activation is a frequent event in adenomas irrespective of karyotype. In contrast, PLAG1 was overexpressed in only 2 of 11 malignant salivary gland tumors analyzed, which suggests that, at least in salivary gland tumors, PLAG1 activation preferentially occurs in benign tumors. PLAG1 over-expression was also found in three of nine mesenchymal tumors, i.e., in two uterine leiomyomas and one leiomyosarcoma. RNase protection, rapid amplification of 5'-cDNA ends (5'-RACE), and reverse transcription-PCR analyses of five adenomas with a normal karyotype revealed fusion transcripts in three tumors. Nucleotide sequence analysis of these showed that they contained fusions between PLAG1 and CTNNB1 (one case) or PLAG1 and a novel fusion partner gene, i.e., the gene encoding the transcription elongation factor SII (two cases). The fusions occurred in the 5' noncoding region of PLAG1, leading to exchange of regulatory control elements and, as a consequence, activation of PLAG1 gene expression. Because all of the cases had grossly normal karyotypes, the rearrangements must result from cryptic rearrangements. The results suggest that in addition to chromosomal translocations and cryptic rearrangements, PLAG1 may also be activated by mutations or indirect mechanisms. Our findings establish a conserved mechanism of PLAG1 activation in salivary gland tumors with and without 8q12 aberrations, which indicates that such activation is a frequent event in these tumors.
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PMID:Conserved mechanism of PLAG1 activation in salivary gland tumors with and without chromosome 8q12 abnormalities: identification of SII as a new fusion partner gene. 1002 85

Because the Wnt-4, -7b, and -11 genes are expressed in metanephric kidneys and code for secreted glycoproteins that may serve as mediators of the transformation of renal mesenchyme to epithelium, we investigated the pattern of Wnt gene expression in late metanephrogenesis and after ureteral obstruction. Newborn and 10-, 20-, and 60-day-old rats underwent complete unilateral ureteral ligation or sham operation. The kidneys were collected bilaterally 1, 5, 10, 20, or 30 days later. RNase protection assays were used to quantify the amounts of mRNA encoding Wnt-4, -7b, and -11, E-cadherin, and cytokeratin-19. Renal development was assessed by histologic characterization of vimentin, cytokeratin, E-cadherin, and beta-catenin distribution. During normal development, the amounts of mRNA encoding Wnt-4 and Wnt-11 increased during gestation and then abruptly decreased after the completion of metanephrogenesis, 15 days after birth. In contrast, the amounts of mRNA encoding Wnt-7b, E-cadherin, and cytokeratin-19 increased during development and into adulthood. In neonatally obstructed kidneys, the expression of Wnt-4 was abnormally maintained when obstruction was induced before the completion of renal development and was reactivated when obstruction was induced after the completion of metanephrogenesis. Wnt-7b expression was minimally affected and Wnt-11 expression was only transiently affected by obstruction. In neonatally obstructed kidneys, the differentiation of mesenchyme to epithelium failed to proceed normally, with the majority of cells maintaining vimentin expression and some differentiated epithelial cells reverting to vimentin expression. In addition, the expression of E-cadherin and cytokeratin was increased in epithelial cells. Changes in the expression of Wnt genes were correlated with histologic changes. This study suggests that Wnt-4 and -11 are likely to be important mediators of the transformation of mesenchyme to epithelium in the kidney. Obstruction induced during metanephrogenesis disrupts the normal pattern of Wnt-4, -7b, and -11 expression and interferes with the normal transformation process in developing kidneys, by maintaining the mesenchymal component and inducing the transformation of epithelium to mesenchyme.
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PMID:Expression of the Wnt gene family during late nephrogenesis and complete ureteral obstruction. 1037 7

TCF proteins are architectural transcription factors that bind to beta-catenin when the Wnt signaling pathway is activated. TCF-1 is specifically expressed in T-cell lineages and its interaction with beta-catenin is thought to be critical for early T-cell development. However, the mechanisms underlying activation of TCF-1 during T-cell development are not completely understood. With the aim of developing RNA aptamers that bind to TCF-1 and regulate its activity, we screened an RNA library consisting of random sequences of 70 nucleotides and were able to isolate aptamers that bind to TCF-1 with high affinity and specificity. We employed RNase footprinting to characterize the RNA structures and map their binding sites for TCF-1. It is hoped that the selected aptamers will regulate TCF-1 activity in vivo, thereby providing a unique tool for modulating TCF-1 function in early T-cell development.
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PMID:In vitro selection and characterization of TCF-1 binding RNA aptamers. 1505 46

Identifying molecular changes that predict the risk for developing colon cancer is critical for designing effective prevention strategies. In the present study, we determined early-stage molecular alterations within the colonic epithelium of A/J and AKR/J mice that are sensitive and resistant to Azoxymethane (AOM)-initiated tumor development, respectively. Six week-old male mice were injected intraperitoneally with AOM (10 mg/kg body weight) once a week for six weeks. One week after the last injection, distal colons from both strains were analyzed for cell proliferation using a proliferating cell nuclear antigen (PCNA) assay. Unlike AKR/J, a significant increase (2.5-fold, p<0.05) in the number of PCNA-positive cells within the upper third of the crypt compartment was observed in the A/J colons. This proliferative response was associated with a sizeable increase in the levels of c-myc mRNA, quantified by RNase protection assay. cDNA sequencing, protein expression and localization of beta-catenin, an upstream activator of c-myc, however, showed no aberrant changes within AOM-exposed A/J colons. Interestingly, TdT-mediated dUTP nick-end labeling assay revealed a significant increase (4-fold) in the number of apoptotic colonocytes in A/J mice following AOM treatment. Consistent with this finding, a modest increase in the expression of pro-apoptotic Bak was limited to the sensitive A/J colons. In summary, the current study suggests that a significant alteration in the rate of cell turnover in the normal appearing colonic mucosa, as observed in susceptible A/J mice, may be one of the earliest events predisposing the colon to neoplastic growth.
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PMID:Strain-specific homeostatic responses during early stages of Azoxymethane-induced colon tumorigenesis in mice. 1778 15

Systemic sclerosis (SSc) is a complex human disorder characterized by progressive skin fibrosis. To better understand the molecular basis of dermal fibrosis in SSc, we analyzed microarray gene expression in skin of the Tight-skin (Tsk) mouse, an animal model where skin fibrosis is caused by an in-frame duplication in fibrillin-1 (Fbn-1). Tsk skin showed increased mRNA levels of several genes involved in Wnt signaling, including Wnt2, Wnt9a, Wnt10b and Wnt11; Dapper homolog antagonist of beta-catenin (DACT1) and DACT2; Wnt-induced secreted protein 2; and secreted frizzled-related protein (SFRP)2 and SFRP4. RNase protection and northern blot confirmed microarray results. Furthermore, Wnt3a markedly stimulated matrix assembly of microfibrillar proteins, including Fbn-1, by cultured fibroblasts, suggesting that Wnts contribute to increased microfibrillar matrices in Tsk skin. Further analysis showed that SFRP4 expression is specifically increased in tissues expressing Tsk-Fbn-1, such as skeletal muscle and skin. The increase in SFRP4 mRNA in Tsk skin started 2 weeks after birth, following the increase in Wnt2 mRNA that occurred at birth. This suggests that SFRP4 may modulate Wnt functions in Tsk skin fibrosis. Lesional skin from SSc patients also showed large increases in SFRP4 mRNA and protein levels in the deep dermis compared to healthy skin, suggesting that the Wnt pathway might regulate skin fibrosis in SSc.
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PMID:Increased expression of Wnt2 and SFRP4 in Tsk mouse skin: role of Wnt signaling in altered dermal fibrillin deposition and systemic sclerosis. 1794 83