Cyclophilin E (CypE) Functions as a Positive Regulator in Osteoblast Differentiation by Regulating the Transcriptional Activity of Runx2.

Cyclophilin E (CypE) belongs to the cyclophilin family and exhibits peptidyl-prolyl isomerase (PPIase) activity. It participates in various biological processes through the regulation of peptidyl-prolyl isomerization. However, the specific role of CypE in osteoblast differentiation has not yet been elucidated.

Cyclophilin A Promotes Osteoblast Differentiation by Regulating Runx2.

Cyclophilin A (CypA) is a ubiquitously expressed and highly conserved protein with peptidyl-prolyl isomerase activity that is involved in various biological activities by regulating protein folding and trafficking. Although CypA has been reported to positively regulate osteoblast differentiation, the mechanistic details remain largely unknown. In this study, we aimed to elucidate the mechanism of CypA-mediated regulation of osteoblast differentiation.

PKC-β modulates Ca mobilization through Stim1 phosphorylation.

Background: Calcium ions play a pivotal role in cell proliferation, differentiation, and migration. Under basal conditions, the calcium level is tightly regulated; however, cellular activation by growth factors increase the ion level through calcium pumps in the plasma membrane and endoplasmic reticulum for calcium signaling. Orai1 is a major calcium channel in the cell membrane of non-excitable cells, and its activity depends on the stromal interaction molecule 1 (Stim1).

Regulation of toll-like receptors expression in muscle cells by exercise-induced stress.

Objective: This study investigates the expression patterns of toll-like receptors (TLRs) and intracellular mediators in horse muscle cells after exercise, and the relationship between TLRS expression in stressed horse muscle cells and immune cell migration toward them.

Methods: The expression patterns of the TLRs (TLR2, TLR4, and TLR8) and downstream signaling pathway-related genes (myeloid differentiation primary response 88 [MYD88]; activating transcription factor 3 [ATF3]) are examined in horse tissues, and horse peripheral blood mononuclear cells (PBMCs), polymorphonuclear cells (PMNs) and muscles in response to exercise, using the quantitative reverse transcription-polymerase chain reaction (qPCR). Expressions of chemokine receptor genes, i.

Role of RS-1 derivatives in homology-directed repair at the human genome ATG5 locus.

Genome editing is a useful tool in basic and clinical research. Among the several approaches used in genome editing, the CRISPR-Cas9 system using clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated protein 9 (Cas9) along with a guide RNA has been developed recently. The CRISPR/Cas9 system induces site-specific double-stranded DNA breaks, which result in DNA repair via non-homologous end joining (NHEJ) or homology-directed repair (HDR).

DPP-4 inhibition enhanced renal tubular and myocardial GLP-1 receptor expression decreased in CKD with myocardial infarction.

Background: Chronic kidney disease (CKD) is strongly associated with cardiovascular disease and is a significant risk factor for increased morbidity and mortality. In contrast, GLP-1 receptor (GLP-1R) activation has been shown to confer both renal and cardiovascular protection, though its relationship with CKD and CKD with myocardial ischemia/reperfusion (MI/R) remains poorly understood. Here, we investigated changes in renal and myocardial GLP-1R expression in the CKD rat model with MI/R.

Modulation of store-operated calcium entry and nascent adhesion by p21-activated kinase 1.

Calcium mobilization is necessary for cell movement during embryonic development, lymphocyte synapse formation, wound healing, and cancer cell metastasis. Depletion of calcium in the lumen of the endoplasmic reticulum using inositol triphosphate (IP3) or thapsigargin (TG) is known to induce oligomerization and cytoskeleton-mediated translocation of stromal interaction molecule 1 (STIM1) to the plasma membrane, where it interacts with the calcium release-activated calcium channel Orai1 to mediate calcium influx; this process is referred to as store-operated calcium entry (SOCE). Furthermore, aberrant STIM1 or SOCE regulation is associated with cancer cell motility and metastasis.

Ottogi Inhibits Wnt/β-catenin Signaling by Regulating Cell Membrane Trafficking of Frizzled8.

Wnt signaling controls critical developmental processes including tissue/body patterning. Here we report the identification of a novel regulator of Wnt signaling, OTTOGI (OTG), isolated from a large-scale expression screening of human cDNAs in zebrafish embryos. Overexpression of OTG in zebrafish embryos caused dorso-anteriorized phenotype, inhibited the expression of Wnt target genes, and prevented nuclear accumulation of β-catenin.

LAMP-3 (Lysosome-Associated Membrane Protein 3) Promotes the Intracellular Proliferation of Salmonella typhimurium.

Lysosomes are cellular organelles containing diverse classes of catabolic enzymes that are implicated in diverse cellular processes including phagocytosis, autophagy, lipid transport, and aging. Lysosome-associated membrane proteins (LAMP-1 and LAMP-2) are major glycoproteins important for maintaining lysosomal integrity, pH, and catabolism. LAMP-1 and LAMP-2 are constitutively expressed in Salmonella-infected cells and are recruited to Salmonella-containing vacuoles (SCVs) as well as Salmonella-induced filaments (Sifs) that promote the survival and proliferation of the Salmonella.

Induction of clusterin expression by neuronal cell death in Zebrafish.

Clusterin, a protein associated with multiple functions, is expressed in a wide variety of mammalian tissues. Although clusterin is known to be involved in neurodegenerative diseases, ageing, and tumorigenesis, a detailed analysis of the consequences of gain- or loss-of-function approaches has yet to be performed to understand the underlying mechanisms of clusterin functions. Since clusterin levels change in neurological diseases, it is likely that clusterin contributes to cell death and degeneration in general.

Protein kinase a phosphorylates Dlx3 and regulates the function of Dlx3 during osteoblast differentiation.

Protein kinase A (PKA), a serine/threonine kinase, regulates bone formation, and enhances Bone morphogenetic protein (BMP)-induced osteoblast differentiation. However, the mechanisms of how PKA controls the cellular response to BMP are not well known. We investigated the effects of modulating PKA activity during BMP2-induced osteoblast differentiation, and found that PKA regulates the function of Dlx3.

Protein kinase A regulates the osteogenic activity of Osterix.

Osterix belongs to the SP gene family and is a core transcription factor responsible for osteoblast differentiation and bone formation. Activation of protein kinase A (PKA), a serine/threonine kinase, is essential for controlling bone formation and BMP-induced osteoblast differentiation. However, the relationship between Osterix and PKA is still unclear.

Ubiquilin 1 interacts with Orai1 to regulate calcium mobilization.

Store-operated calcium entry (SOCE) channels composed of Stim and Orai proteins play a critical role in diverse biological processes. Upon endoplasmic reticulum (ER)-mediated calcium (Ca(2+)) depletion, Stim proteins oligomerize with Orai to initiate Ca(2+) influx across the plasma membrane. The ubiquitin-like (UBL) and ubiquitin-associated (UBA) domains of ubiquilin 1 are involved in the degradation of presenilin and polyglutamine proteins.

Novel transmembrane protein 126A (TMEM126A) couples with CD137L reverse signals in myeloid cells.

Members of the TNF family can promote signals in myeloid cells and both positively and negatively regulate the production of pro-inflammatory cytokines depending on the target myeloid cell type. Using the yeast-two hybrid system, we identified transmembrane protein 126A (TMEM126A) as a binding partner for CD137L (4-1BB ligand). We found that TMEM126A associated and co-localized with CD137L in a mouse macrophage cell line and knockdown of TMEM126A with siRNA abolished the CD137L-induced tyrosine phosphorylation as well as the up-regulation of M-CSF, IL-1β and TN-C expressions.

PKC signaling inhibits osteogenic differentiation through the regulation of Msx2 function.

Protein kinase C (PKC) signaling regulates osteoblast differentiation, but little is known about its downstream effectors. We examined the effect of modulating PKC activity on osteogenic transcription factors and found that the protein level of Msx2 is affected. Msx2 is induced by osteogenic signals such as BMPs and it plays critical roles in bone formation and osteoblast differentiation.

FGF-2 inhibits TNF-α mediated apoptosis through upregulation of Bcl2-A1 and Bcl-xL in ATDC5 cells.

FGF-2 is involved in cell survival, proliferation, apoptosis, and angiogenesis in a wide variety of cells. FRGRs, PI3K and MAP kinases are well known mediators of FGF signaling. Despite its known roles during many developmental processes, including osteogenesis, there are few known targets of FGF-2.

Activation of the STAT6 transcription factor in Jurkat T-cells by the herpesvirus saimiri Tip protein.

Herpesvirus saimiri (HVS), a T-lymphotropic monkey herpesvirus, induces fulminant T-cell lymphoma in non-natural primate hosts. In addition, it can immortalize human T-cells in vitro. HVS tyrosine kinase-interacting protein (Tip) is an essential viral gene required for T-cell transformation both in vitro and in vivo.

Protein kinase A phosphorylates and regulates the osteogenic activity of Dlx5.

Dlx5 transcription factor plays important roles in osteoblast differentiation and its transcription is regulated by many osteogenic signals including BMP-2. Recent studies suggest that the function of Dlx5 is also regulated post-translationally by protein kinases such as p38 and CaMKII. Protein kinase A (PKA) is involved in several steps of osteoblast differentiation and its activity has been shown necessary, yet not sufficient, for BMP-induced osteoblast differentiation.

Direct interaction of cellular hnRNP-F and NS1 of influenza A virus accelerates viral replication by modulation of viral transcriptional activity and host gene expression.

To investigate novel NS1-interacting proteins, we conducted a yeast two-hybrid analysis, followed by co-immunoprecipitation assays. We identified heterogeneous nuclear ribonucleoprotein F (hnRNP-F) as a cellular protein interacting with NS1 during influenza A virus infection. Co-precipitation assays suggest that interaction between hnRNP-F and NS1 is a common and direct event among human or avian influenza viruses.

Enhanced cytotoxicity of 5-FU by bFGF through up-regulation of uridine phosphorylase 1.

Anti cancer agent 5-FU (Fluoro Uracil) is a prodrug that can be metabolized and then activated to interfere with RNA and DNA homeostasis. However, the majority of administered 5-FU is known to be catabolized in vivo in the liver where Dihydropyrimidine dehydrogenase (DPD) is abundantly expressed to degrade 5-FU. The biological factors that correlate with the response to 5-FU-based chemotherapy have been proposed to include uridine phosphorylase (UPP), thymidine phosphorylase (TPP), p53 and microsatellite instability.

Antibacterial activity of recombinant hCAP18/LL37 protein secreted from Pichia pastoris.

Human antimicrobial peptide CAP18/LL37 (hCAP18/LL37) was expressed in Pichia pastoris and its antibacterial activity was tested against pathogenic bacteria. The full length ORF of hCAP18/LL37 was cloned into the pPICZaA vector followed by integration into the genomic AOX1 gene of P. pastoris.

Jab1/CSN5 induces the cytoplasmic localization and degradation of RUNX3.

Runt-related (RUNX) transcription factors play pivotal roles in neoplastic development and have tissue-specific developmental roles in hematopoiesis (RUNX1), osteogenesis (RUNX2), as well as neurogenesis and thymopoiesis (RUNX3). RUNX3 is a tumor suppressor in gastric carcinoma, and its expression is frequently inactivated by DNA methylation or its protein mislocalized in many cancer types, including gastric and breast cancer. Jun-activation domain-binding protein 1 (Jab1/CSN5), a component of the COP9 signalosome (CSN), is critical for nuclear export and the degradation of several tumor suppressor proteins, including p53, p27(Kip1), and Smad4.

Multi-transmembrane protein K15 of Kaposi's sarcoma-associated herpesvirus targets Lyn kinase in the membrane raft and induces NFAT/AP1 activities.

Viral proteins of gamma-2 herpesviruses, such as LMP2A of Epstein Barr virus (EBV) and Tip of herpesvirus saimiri (HVS) dysregulate lymphocyte signaling by interacting with Src family kinases. K15 open reading frame of Kaposi's sarcoma associated herpesvirus (KSHV), located at the right end of the viral genome, encodes several splicing variants differing in numbers of transmembrane domains. Previously, we demonstrated that the cytoplasmic tail of the K15 protein interfered with B cell receptor signal transduction to cellular tyrosine phosphorylation and calcium mobilization.

Pim-1 kinase phosphorylates and stabilizes RUNX3 and alters its subcellular localization.

The loci of the Pim and Runx gene families have been identified as targets for viral insertions in CD2-myc mice. Synergistic cooperation between Pim and RUNX was also found in the CD2-Runx2 transgenic mouse lymphoma model. RUNX genes have come to prominence recently because of their roles as essential regulators of cell fate in development.

Identification of osteogenic purmorphamine derivatives.

During embryonic and cancer development, the Hedgehog family of proteins, including Sonic Hedgehog, play an important role by relieving the inhibition of Smo by Ptc, thus activating the Smo signaling cascade. Recently, a purine compound, purmorphamine, has been reported to target the Hedgehog signaling pathway by interacting with Smo. Interestingly, both Sonic Hedgehog and purmorphamine were found to promote the osteogenic differentiation of mouse chondroprogenitor cells.