Search results for "Intracellular Signaling Peptides and Proteins"
showing 10 items of 140 documents
Expression of WISPs and of their novel alternative variants in human hepatocellular carcinoma cells
2005
WISPs (Wnt-induced secreted proteins) are members of the CCN (CTGF/Cyr61/Nov) family involved in fibrotic disorders and tumorigenesis. They have a typical structure composed of four conserved cysteine-rich modular domains, but variants of CCN members lacking one or more modules, generated by alternative splicing or gene mutations, have been described in various pathological conditions. WISP genes were first described as downstream targets of the Wnt signaling pathway, which is frequently altered in human hepatocellular carcinoma (HCC). In the present study, WISP mRNA expression was analyzed by RT-PCR in four human HCC cell lines (HepG2, HuH-6, HuH-7, HA22T/VGH). Our results show for the fir…
Inhibitors of Rho-kinase modulate amyloid-β (Aβ) secretion but lack selectivity for Aβ42
2005
Certain non-steroidal anti-inflammatory drugs (NSAIDs) preferentially inhibit production of the amyloidogenic Abeta42 peptide, presumably by direct modulation of gamma-secretase activity. A recent report indicated that NSAIDs could reduce Abeta42 by inhibition of the small GTPase Rho, and a single inhibitor of Rho kinase (ROCK) mimicked the effects of Abeta42-lowering NSAIDs. To investigate whether Abeta42 reduction is a common property of ROCK inhibitors, we tested commercially available compounds in cell lines that were previously used to demonstrate the Abeta42-lowering activity of NSAIDs. Surprisingly, we found that two ROCK inhibitors reduced total Abeta secretion in a dose-dependent m…
Regulated segregation of kinase Dyrk1A during asymmetric neural stem cell division is critical for EGFR-mediated biased signaling.
2010
SummaryStem cell division can result in two sibling cells exhibiting differential mitogenic and self-renewing potential. Here, we present evidence that the dual-specificity kinase Dyrk1A is part of a molecular pathway involved in the regulation of biased epidermal growth factor receptor (EGFR) signaling in the progeny of dividing neural stem cells (NSC) of the adult subependymal zone (SEZ). We show that EGFR asymmetry requires regulated sorting and that a normal Dyrk1a dosage is required to sustain EGFR in the two daughters of a symmetrically dividing progenitor. Dyrk1A is symmetrically or asymmetrically distributed during mitosis, and biochemical analyses indicate that it prevents endocyto…
The Functional Role of the Second NPXY Motif of the LRP1 β-Chain in Tissue-type Plasminogen Activator-mediated Activation of N-Methyl-D-aspartate Rec…
2008
The low density lipoprotein receptor-related protein 1 (LRP1) emerges to play fundamental roles in cellular signaling pathways in the brain. One of its prominent ligands is the serine proteinase tissue-type plasminogen activator (tPA), which has been shown to act as a key activator of neuronal mitogen-activated protein kinase pathways via the N-methyl-D-aspartate (NMDA) receptor. However, here we set out to examine whether LRP1 and the NMDA receptor might eventually act in a combined fashion to mediate tPA downstream signaling. By blocking tPA from binding to LRP1 using the receptor-associated protein, we were able to completely inhibit NMDA receptor activation. Additionally, inhibition of …
Role of humanin, a mitochondrial-derived peptide, in cardiovascular disorders
2020
The mitochondria produce specific peptides-mitochondrial-derived peptides-that mediate the transcriptional stress response by their translocation into the nucleus and interaction with deoxyribonucleic acid. Mitochondrial-derived peptides are regulators of metabolism. This class of peptides comprises humanin, mitochondrial open reading frame of the 12S ribosomal ribonucleic acid type c (MOTS-c) and small humanin-like peptides (SHLPs). Humanin inhibits mitochondrial complex 1 activity and limits the level of oxidative stress in the cell. Data show that mitochondrial-derived peptides have a role in improving metabolic diseases, such as type 2 diabetes. Perhaps humanin can be used as a marker f…
The retinitis pigmentosa protein RP2 links pericentriolar vesicle transport between the Golgi and the primary cilium.
2010
Photoreceptors are complex ciliated sensory neurons. The basal body and periciliary ridge of photoreceptors function in association with the Golgi complex to regulate the export of proteins from the inner segment to the outer segment sensory axoneme. Here, we show that the retinitis pigmentosa protein RP2, which is a GTPase activating protein (GAP) for Arl3, localizes to the ciliary apparatus, namely the basal body and the associated centriole at the base of the photoreceptor cilium. Targeting to the ciliary base was dependent on N-terminal myristoylation. RP2 also localized to the Golgi and periciliary ridge of photoreceptors, which suggested a role for RP2 in regulating vesicle traffic an…
Cabut/dTIEG associates with the transcription factor Yorkie for growth control
2015
The Drosophila transcription factor Cabut/dTIEG (Cbt) is a growth regulator, whose expression is modulated by different stimuli. Here, we determine Cbt association with chromatin and identify Yorkie (Yki), the transcriptional co-activator of the Hippo (Hpo) pathway as its partner. Cbt and Yki co-localize on common gene promoters, and the expression of target genes varies according to changes in Cbt levels. Down-regulation of Cbt suppresses the overgrowth phenotypes caused by mutations in expanded (ex) and yki overexpression, whereas its up-regulation promotes cell proliferation. Our results imply that Cbt is a novel partner of Yki that is required as a transcriptional co-activator in growth…
Reorganization of Nuclear Domain 10 Induced by Papillomavirus Capsid Protein L2
2002
AbstractNuclear domains (ND) 10 are associated with proteins implicated in transcriptional regulation, growth suppression, and apoptosis. We now show that the minor capsid protein L2 of human papillomavirus (HPV) type 33 induces a reorganization of ND10-associated proteins. Whereas the promyelocytic leukemia protein, the major structural component of ND10, was unaffected by L2, Sp100 was released from ND10 upon L2 expression. The total cellular amount of Sp100, but not of Sp100 mRNA, decreased significantly, suggesting degradation of Sp100. Proteasome inhibitors induced the dispersal of Sp100 and inhibited the nuclear translocation of L2. In contrast to Sp100, Daxx was recruited to ND10 by …
Heat shock and Cd2+ exposure regulate PML and Daxx release from ND10 by independent mechanisms that modify the induction of heat-shock proteins 70 an…
2003
Nuclear domains called ND10 or PML bodies might function as nuclear depots by recruiting or releasing certain proteins. Although recruitment of proteins through interferon-induced upregulation and SUMO-1 modification level of PML had been defined, it is not known whether release of proteins is regulated and has physiological consequences. Exposure to sublethal environmental stress revealed a sequential release of ND10-associated proteins. Upon heat shock Daxx and Sp100 were released but PML remained, whereas exposure to subtoxic concentrations of CdCl2 induced the release of ND10-associated proteins, including PML, with Sp100 remaining in a few sites. In both cases,recovery times were simil…
Regulation of ribonucleotide reductase in response to iron deficiency
2011
Ribonucleotide reductase (RNR) is an essential enzyme required for DNA synthesis and repair. Although iron is necessary for class Ia RNR activity, little is known about the mechanisms that control RNR in response to iron deficiency. In this work, we demonstrate that yeast cells control RNR function during iron deficiency by redistributing the Rnr2–Rnr4 small subunit from the nucleus to the cytoplasm. Our data support a Mec1/Rad53-independent mechanism in which the iron-regulated Cth1/Cth2 mRNA-binding proteins specifically interact with the WTM1 mRNA in response to iron scarcity, and promote its degradation. The resulting decrease in the nuclear-anchoring Wtm1 protein levels leads to the re…