Search results for "Repressor Protein"
showing 10 items of 169 documents
Telomere Length Determines TERRA and R-Loop Regulation through the Cell Cycle
2017
Maintenance of a minimal telomere length is essential to prevent cellular senescence. When critically short telomeres arise in the absence of telomerase, they can be repaired by homology-directed repair (HDR) to prevent premature senescence onset. It is unclear why specifically the shortest telomeres are targeted for HDR. We demonstrate that the non-coding RNA TERRA accumulates as HDR-promoting RNA-DNA hybrids (R-loops) preferentially at very short telomeres. The increased level of TERRA and R-loops, exclusively at short telomeres, is due to a local defect in RNA degradation by the Rat1 and RNase H2 nucleases, respectively. Consequently, the coordination of TERRA degradation with telomere r…
E4BP4/NFIL3 modulates the epigenetically repressed RAS effector RASSF8 function through histone methyltransferases
2018
RAS proteins are major human oncogenes, and most of the studies are focused on enzymatic RAS effectors. Recently, nonenzymatic RAS effectors (RASSF, RAS association domain family) have garnered special attention because of their tumor-suppressive properties in contrast to the oncogenic potential of the classical enzymatic RAS effectors. Whereas most members of RASSF family are deregulated by promoter hypermethylation, RASSF8 promoter remains unmethylated in many cancers but the mechanism(s) of its down-regulation remains unknown. Here, we unveil E4BP4 as a critical transcriptional modulator repressing RASSF8 expression through histone methyltransferases, G9a and SUV39H1. In line with these …
MiR-24 induces chemotherapy resistance and hypoxic advantage in breast cancer
2017
// Giuseppina Roscigno 1, 2, * , Ilaria Puoti 1, 2, * , Immacolata Giordano 1 , Elvira Donnarumma 3 , Valentina Russo 1 , Alessandra Affinito 1 , Assunta Adamo 1 , Cristina Quintavalle 1, 2 , Matilde Todaro 4 , Maria dM Vivanco 5 , Gerolama Condorelli 1, 2 1 Department of Molecular Medicine and Medical Biotechnology, “Federico II” University of Naples, Naples, Italy 2 IEOS, CNR, Naples, Italy 3 IRCCS-SDN, Naples, Italy 4 Department of Pathobiology and Medical Biotechnology, University of Palermo, Palermo, Italy 5 CIC bioGUNE, Centre for Cooperative Research in Biosciences, Derio, Spain * These authors have contributed equally to the paper as first authors Correspondence to: Gerolama Condore…
Congenital undifferentiated sarcoma associated to BCOR-CCNB3 gene fusion
2017
Small round cell sarcomas are aggressive bone and soft tissue tumors that predominantly affect children and young adults. A new group of sarcomas with a recurrent BCOR-CCNB3 gene fusion has been recently identified in previously unclassifiable small round cell sarcomas. BCOR-CCNB3 sarcomas share clinical and pathologic similarities with Ewing sarcoma, but show a stronger male predilection and less aggressiveness, as well as distinct gene expression profiling and pangenomic SNP array analyses. We report the unusual case of a congenital BCOR-CCNB3 retroperitoneal sarcoma in a female born at 34th gestational week, which was diagnosed in necropsy after 21hours of life. Immunohistochemical analy…
Incomplete penetrance and phenotypic variability of 6q16 deletions including SIM1.
2015
International audience; 6q16 deletions have been described in patients with a Prader-Willi-like (PWS-like) phenotype. Recent studies have shown that certain rare single-minded 1 (SIM1) loss-of-function variants were associated with a high intra-familial risk for obesity with or without features of PWS-like syndrome. Although SIM1 seems to have a key role in the phenotype of patients carrying 6q16 deletions, some data support a contribution of other genes, such as GRIK2, to explain associated behavioural problems. We describe 15 new patients in whom de novo 6q16 deletions were characterised by comparative genomic hybridisation or single-nucleotide polymorphism (SNP) array analysis, including…
Screening for Autoantibodies to Tissue Transglutaminase Reveals a Low Prevalence of Celiac Disease in Blood Donors with Cryptogenic Hypertransaminase…
2001
Patients with chronic cryptogenic hypertransaminasemia are at high risk of developing celiac disease (CD). In fact, among the various serological disorders, CD patients at onset frequently present hypertransaminasemia. In this study, we evaluated usefulness and reliability of the new test for antitissue transglutaminase (tTG) in screening for CD as well as in estimating the prevalence of CD in a population of blood donors presenting unexplained hypertransaminasemia at donation. Controls were 180 consecutive healthy donors without hypertransaminasemia and 20 CD patients with known antiendomysial antibody (EmA) positivity. Out of 22,204 blood donors over a period of 2 years, we found 258 subj…
Cloning of the human NCNF gene.
1998
We have cloned from a cDNA library of human testis tissue the human homologue to the mouse nuclear orphan receptor NCNF (neuronal cell nuclear factor). The open reading frame encodes a protein of 480 amino acids, the sequence of which (EMBL accession no. X99975) is 98.3% identical to the mouse homologue. Northern blot analysis of adult human tissues revealed a broad pattern of tissue expression. Similar to NCNF expression in mouse testis, two transcript forms of the single copy gene are expressed in human tissues. The two transcript forms which differ only in their 3'UTR, result in human from differential polyadenylation, in mouse from alternative splicing. Based on the high level of sequen…
BRAF(V600E) mutation influences hypoxia-inducible factor-1alpha expression levels in papillary thyroid cancer
2010
Abstract Hypoxia-inducible factor-1alpha is found frequently overexpressed in solid tumors cells, exerting an important role in angiogenesis, glucose metabolism, cell proliferation, survival and invasion. In thyroid carcinomas, hypoxia-inducible factor-1alpha expression was found increased in differentiated, poorly differentiated, medullary and anaplastic variants. Hypoxia represents the principal stimulus responsible for hypoxia-inducible factor-1alpha induction. Other nonhypoxic stimuli increase hypoxia-inducible factor-1alpha synthesis through the activation of phosphatidylinositol 3-kinase and mitogen-activated protein kinase pathways in a cell-type-specific manner. We have previously s…
Ten novel mutations found in Aniridia.
1998
Aniridia (AN) is a sight-threatening congenital ocular disorder characterized by iris hypoplasia, corneal pannus, foveal and optic nerve hypoplasia, cataract formation, and glaucoma. In two-thirds of the patients, AN is inherited in an autosomal dominant fashion with almost complete penetrance but variable expression. The remaining cases are sporadic. Aniridia has been shown to be associated with mutations in the PAX6 gene, located on chromosome 11p13, telomeric to the Wilms' tumor predisposition gene (WT1). This paper describes 14 mutations in the PAX6 gene in patients with AN. Among these 14 mutations, 10 have been unpublished until now. They result most probably in haploinsufficiency and…
Variable pulmonary manifestations in Chitayat syndrome: Six additional affected individuals
2020
Hand hyperphalangism leading to shortened index fingers with ulnar deviation, hallux valgus, mild facial dysmorphism and respiratory compromise requiring assisted ventilation are the key features of Chitayat syndrome. This condition results from the recurrent heterozygous missense variant NM_006494.2:c.266A>G; p.(Tyr89Cys) in ERF on chromosome 19q13.2, encoding the ETS2 repressor factor (ERF) protein. The pathomechanism of Chitayat syndrome is unknown. To date, seven individuals with Chitayat syndrome and the recurrent pathogenic ERF variant have been reported in the literature. Here, we describe six additional individuals, among them only one presenting with a history of assisted ventil…