Search results for "nuclear localization"
showing 10 items of 30 documents
Identification of a classic nuclear localization signal at the N terminus that regulates the subcellular localization of Rbfox2 isoforms during diffe…
2016
Nuclear localization of the alternative splicing factor Rbfox2 is achieved by a C-terminal nuclear localization signal (NLS) which can be excluded from some Rbfox2 isoforms by alternative splicing. While this predicts nuclear and cytoplasmic localization, Rbfox2 is exclusively nuclear in some cell types. Here, we identify a second NLS in the N terminus of Rbfox2 isoform 1A that is not included in Rbfox2 isoform 1F. Rbfox2 1A isoforms lacking the C-terminal NLS are nuclear, whereas equivalent 1F isoforms are cytoplasmic. A shift in Rbfox2 expression toward cytoplasmic 1F isoforms occurs during epithelial to mesenchymal transition (EMT) and could be important in regulating the activity and fu…
Differential subcellular expression of P525LFUS as a putative biomarker for ALS phenoconversion
2020
P525LFused-in-Sarcoma ( FUS ) mutation is associated with a specific amyotrophic lateral sclerosis (ALS) phenotype characterized by a juvenile-onset and a severe course.1 This harmful point mutation is located in the nuclear localization signal (NLS) domain at the protein C-terminal.2 Although wild-type FUS protein is expressed almost exclusively in the nucleus, the P525L FUS mutation leads to a protein mislocalization into the cytoplasm3,4 because of its loss of capacity to bind its transporter karyopherin-2 and to be transferred back to the nucleus.3
Hypoxia-Induced miR-675-5p Supports β-Catenin Nuclear Localization by Regulating GSK3-β Activity in Colorectal Cancer Cell Lines
2020
The reduction of oxygen partial pressure in growing tumors triggers numerous survival strategies driven by the transcription factor complex HIF1 (Hypoxia Inducible Factor-1). Recent evidence revealed that HIF1 promotes rapid and effective phenotypic changes through the induction of non-coding RNAs, whose contribution has not yet been fully described. Here we investigated the role of the hypoxia-induced, long non-coding RNA H19 (lncH19) and its intragenic miRNA (miR-675-5p) into HIF1-Wnt crosstalk. During hypoxic stimulation, colorectal cancer cell lines up-regulated the levels of both the lncH19 and its intragenic miR-675-5p. Loss of expression experiments revealed that miR-675-5p inhibitio…
Protoparvovirus Knocking at the Nuclear Door
2017
Protoparvoviruses target the nucleus due to their dependence on the cellular reproduction machinery during the replication and expression of their single-stranded DNA genome. In recent years, our understanding of the multistep process of the capsid nuclear import has improved, and led to the discovery of unique viral nuclear entry strategies. Preceded by endosomal transport, endosomal escape and microtubule-mediated movement to the vicinity of the nuclear envelope, the protoparvoviruses interact with the nuclear pore complexes. The capsids are transported actively across the nuclear pore complexes using nuclear import receptors. The nuclear import is sometimes accompanied by structural chan…
Phosphorylation of cytochromes P450: First discovery of a posttranslational modification of a drug-metabolizing enzyme
2005
Cytochromes P450 (CYP) are important components of xenobiotic-metabolizing monooxygenases (CYP-dependent monooxygenases). Their regulation by induction, most commonly by transcriptional activation, mediated by xenobiotics, normally substrates of the corresponding CYP, is well known and has been widely studied. Our team has discovered an additional important regulation of xenobiotic-metabolizing CYPs pertaining to posttranslational modification by phosphorylation. Individual CYPs are phosphorylated by different protein kinases, leading to CYP isoenzyme-selective changes in the metabolism of individual substrates and consequent drastic changes in the control of genotoxic metabolites. Best stu…
Survivin’s Dual Role: An Export’s View
2007
Survivin is proposed to function as a mitotic regulator and an apoptosis inhibitor during development and pathogenesis. As such, survivin has aroused keen interest in disparate areas of basic and translational research. Survivin acts as a subunit of the chromosomal passenger complex (CPC), composed of the mitotic kinase Aurora-B, Borealin and INCENP, and is essential for proper chromosome segregation and cytokinesis. Our recent findings indicate that the nuclear export receptor Crm1 is critically involved in tethering the CPC to the centromere by interacting with a leucine-rich nuclear export signal (NES), evolutionary conserved in all mammalian survivin proteins. In addition, the survivin/…
Characterization of a nuclear localization signal of canine parvovirus capsid proteins.
1998
We investigated the abilities of synthetic peptides mimicking the potential nuclear localization signal of canine parvovirus (CPV) capsid proteins to translocate a carrier protein to the nucleus following microinjection into the cytoplasm of A72 cells. Possible nuclear localization sequences were chosen for synthesis from CPV capsid protein sequences (VP1, VP2) on the basis of the presence of clustered basic residues, which is a common theme in most of the previously identified targeting peptides. Nuclear targeting activity was found within the N-terminal residues 4-13 (PAKRARRGYK) of the VP1 capsid protein. While replacement of Arg10 with glycine did not affect the activity, replacement of…
Mutation Analysis of Core Binding Factor A1 in Patients with Cleidocranial Dysplasia
1999
SummaryCleidocranial dysplasia (CCD) is a dominantly inherited disorder characterized by patent fontanelles, wide cranial sutures, hypoplasia of clavicles, short stature, supernumerary teeth, and other skeletal anomalies. We recently demonstrated that mutations in the transcription factor CBFA1, on chromosome 6p21, are associated with CCD. We have now analyzed the CBFA1 gene in 42 unrelated patients with CCD. In 18 patients, mutations were detected in the coding region of the CBFA1 gene, including 8 frameshift, 2 nonsense, and 9 missense mutations, as well as 2 novel polymorphisms. A cluster of missense mutations at arginine 225 (R225) identifies this residue as crucial for CBFA1 function. …
Calmodulin binds to p21(Cip1) and is involved in the regulation of its nuclear localization.
1999
p21(Cip1), first described as an inhibitor of cyclin-dependent kinases, has recently been shown to have a function in the formation of cyclin D-Cdk4 complexes and in their nuclear translocation. The dual behavior of p21(Cip1) may be due to its association with other proteins. Different evidence presented here indicate an in vitro and in vivo interaction of p21(Cip1) with calmodulin: 1) purified p21(Cip1) is able to bind to calmodulin-Sepharose in a Ca(2+)-dependent manner, and this binding is inhibited by the calmodulin-binding domain of calmodulin-dependent kinase II; 2) both molecules coimmunoprecipitate when extracted from cellular lysates; and 3) colocalization of calmodulin and p21(Cip…
DNA binding of L1 is required for human papillomavirus morphogenesis in vivo.
2002
AbstractThe role of putative DNA-binding domains of human papillomavirus (HPV) capsid proteins for DNA encapsidation in vivo is still unknown. We have now analyzed mutants of the major capsid protein L1 of HPV type 33, which are defective for DNA binding, for their ability to encapsidate DNA using an in vivo packaging approach. Since the DNA-binding domain and the nuclear localization signal (NLS) of L1 overlap, both a carboxy-terminal deletion mutant (L1-1/470) and a substitution mutant (L1-1/477M9) were analyzed. L1-1/477M9 has the classical NLS replaced by a noncanonical NLS taken from the human hnRNP protein A1. The mutant proteins were defective for DNA binding in contrast to wild-type…