Bisphenol A (BPA) is putatively regarded as an environmental neurotoxicant found in everyday plastic products and materials, however, the possible neurobehavioral adverse consequences molecular mechanisms animals have not been clearly characterized. The nematode Caenorhabditis elegans has become a promising animal model for neurotoxicological researches. To investigate dose-effect relationships of BPA-induced neurotoxicity effects, locomotion behavior developmental parameters were determined...

Paeoniflorin (PF) is a monoterpene glycoside extracted from the root of Paeonia lactiflora Pall. Previous studies have demonstrated that PF inhibits growth, invasion, and metastasis tumors in vivo vitro. However, effect on hypoxia-induced epithelial-mesenchymal transition (EMT) breast cancer cells remains unknown. Therefore, objective this study was to investigate EMT cells, as well characterize underlying mechanism. The results presented demonstrate blocks migration invasion by repressing...

Abstract The theories for substrate recognition in enzyme catalysis have evolved from lock-key to induced fit, then conformational selection, and selection followed by fit. However, the prevalence consensus of these require further examination. Here we use cryogenic electron microscopy African swine fever virus type 2 topoisomerase ( Asfv Top2) demonstrate binding a joint ordered manner: catalytic enzyme, substrates, apo - Top2 pre-exists six conformers that comply with two-gate mechanism...

The nematode Caenorhabditis elegans has been shown to be a model organism in studying aquatic toxicity. Although epidemiological studies have that arsenic is teratogenic and carcinogenic humans, the lethality assay indicated C. less sensitive inorganic than any other organisms tested thus far. In present study, we used more malleable germline of as an vivo system investigate genotoxic effects arsenite. After animals were exposed sodium arsenite at concentrations ranging from 1 μM 0.5 mM,...

The transition metal cadmium (Cd) has been shown to induce apoptosis in a variety of cell lines and tissues. Caspase activation the tumor suppressor gene p53 mitogen-activated protein kinase (MAPK) signaling cascades have reported be involved Cd-induced apoptosis. However, underlying pathways not clearly elucidated vivo systems, primarily for lack appropriate animal models. nematode Caenorhabditis elegans good model study basic biological processes, including In this study, we used mutated...

The forkhead-associated (FHA) domain recognizes phosphothreonine (pT) with high specificity and functional diversity. TIFA (TRAF-interacting protein an FHA domain) is the smallest FHA-containing human protein. Its overexpression was previously suggested to provoke NF-κB activation, yet its exact roles in this signaling pathway underlying molecular mechanism remain unclear. Here we identify a novel threonine phosphorylation site on show that phosphorylated binds of TIFA, leading...

The tristetraprolin (TTP) family of mRNA-binding proteins contains three major members, Ttp, Zfp36l1, and Zfp36l2. Ttp down-regulates the stability AU-rich element-containing mRNAs functions as an anti-inflammation regulator.To examine whether other TTP also play roles in inflammatory response, their expression profiles possible mRNA targets were determined knockdown cells.Ttp protein highly induced by lipopolysaccharide (LPS), whereas Zfp36l1 Zfp36l2 down-regulated phosphorylated during...

Hepatotoxin microcystin-LR (MC-LR) can induce apoptosis in a variety of cells. However, the underlying pathways MC-LR-induced have not been well elucidated yet. To find out roles signaling response to MC-LR, germ cell corpses were scored Caenorhabditis elegans N2 wild type and strains carrying mutated alleles homologous their mammalian counterparts. We found that exposure MC-LR at 1.0 μg/L significantly increased germline N2. Germline was absent all doses ced-3 ced-4 loss-of-function...

Background Turnover of mRNA is a critical step in the regulation gene expression, and an important decay removal 5′ cap. We previously demonstrated that expression some immediate early mRNAs controlled by RNA stability during differentiation 3T3-L1 preadipocytes. Methodology/Principal Findings Here we show mouse decapping protein Dcp1a phosphorylated via ERK signaling pathway Mass spectrometry analysis site-directed mutagenesis combined with kinase assay identified pathway–mediated dual...

Ribosome biogenesis governs protein synthesis. NIFK is transactivated by c-Myc, the key regulator of ribosome biogenesis. The biological function human not well established, except that it has been shown to interact with Ki67 and NPM1. Here we report required for cell cycle progression participates in via its RNA recognition motif (RRM). We show silencing inhibits proliferation through a reversible p53-dependent G1 arrest, possibly induction RPL5/RPL11-mediated nucleolar stress....

Abstract Plant transporters regulating the distribution of secondary metabolites play critical roles in defending against pathogens, insects, and interacting with beneficial microbes. The phosphorylation these can alter their activity, stability, intracellular protein trafficking. However, regulatory mechanism underlying this modification remains elusive. In study, we discovered two orthologs mammalian PKA, PKG, PKC (AGC) kinases, oxidative signal-inducible 1 (OXI1) its closest homologue,...

Tristetraprolin binds mRNA AU-rich elements and thereby facilitates the destabilization of mature in cytosol.To understand how tristetraprolin mechanistically functions, we biopanned with a phage-display library for proteins that interact retrieved, among others, fragment poly(A)-binding protein nuclear 1, which assists 3'-polyadenylation by binding to immature poly(A) tails increases activity polymerase, is directly responsible polyadenylation. The tristetraprolin/poly(A)-binding 1...

The cell cycle checkpoint kinases play central roles in the genome maintenance of eukaryotes. Activation yeast kinase Rad53 involves Rad9 or Mrc1 adaptor-mediated phospho-priming by Mec1 kinase, followed auto-activating phosphorylation within its activation loop. However, mechanisms which these adaptors regulate priming specific sites and how this then leads to remain poorly understood. Here we used quantitative mass spectrometry delineate stepwise events endogenous response S phase...

Progestin and adipoQ receptor family member III (PAQR3), a of the PAQR family, is frequently downregulated in different types human cancer. However, its expression functions esophageal cancer are still unknown. This study aimed to explore PAQR3 cell lines investigate role development Our data showed that expressed low amounts lines. Overexpression significantly suppressed proliferation, migration, invasion cells. In addition, overexpression protein levels RAF1, p-MEK1, p-ERK1/2 Furthermore,...

Many studies have shown that arsenite is a potent inducer of apoptosis both in cells and tissues. However, there lack appropriate vivo animal models to study the underlying mechanisms arsenite-induced apoptosis. Caenorhabditis elegans an excellent model organism for studying many biological processes. We showed previously C. could be used as system investigate genotoxic effects arsenite. In order elucidate vivo, present study, we mutated alleles homologue known mammalian genes are involved...

Calumenin isoforms 1 and 2 (calu-1/2), encoded by the CALU gene, belong to CREC protein family. Calu-1/2 proteins are secreted into extracellular space, but secretory process regulatory mechanism largely unknown. Here, using a time-lapse imaging system, we visualized intracellular transport of calu-1/2-EGFP after their translocation ER lumen. Interestingly, observed that an abundance accumulated in cellular processes before being released while only part were directly attaching cell...

Bisphenol A can trigger germline apoptosis<italic>via</italic>three signaling pathways including DNA damage response (DDR) pathway, mitogen-activated protein kinase (MAPK) cascades and insulin-like growth factor-1 (IGF-1) network in<italic>Caenorhabditis elegans</italic>.

The aim of the present study was to evaluate effect Tob1 on radiosensitivity breast cancer cells. results showed that overexpression reduced clonogenic growth 231 cells and induced rate apoptosis. caused an accumulation in G0 /G1 phase decreased percentage S phase. We also found significantly phosphorylation JNK p38. activator p38, anisomycin, attenuated blockage cell cycle reversed Taken together, enhanced through regulation p38 pathways. indicated might be a promising molecular gene...