Vascular endothelial growth factor (VEGF) plays a significant role in blood-brain barrier breakdown and angiogenesis after brain injury. VEGF-induced cell migration is key step the angiogenic response mediated by an accelerated rate of focal adhesion complex assembly disassembly. In this study, we identified signaling mechanisms which VEGF regulates human microvascular (HBMEC) integrity adhesions, complexes comprised scaffolding proteins organized to extracellular matrix. We found that...

Abstract The integrity of the blood-brain barrier (BBB) is critical for normal brain function. Neuropathological abnormalities in AIDS patients have been associated with perivascular HIV-infected macrophages, gliosis, and permeability BBB. processes by which HIV causes these pathological conditions are not well understood. To characterize mechanism HIV-1 Tat protein modulates human microvascular endothelial cell (HBMEC) functions, we studied effects modulating HBMEC apoptosis permeability....

The nuclear matrix is defined as the insoluble framework of nucleus and has been implicated in regulation gene expression, cell cycle, structural integrity via linkage to intermediate filaments cytoskeleton. We have discovered a novel protein, NRP/B (nuclear restricted protein/brain), which contains two major elements: BTB domain–like structure predicted NH2 terminus, “kelch motif” COOH-terminal domain. mRNA (5.5 kb) predominantly expressed human fetal adult brain with minor expression...

Human artificial chromosome (HAC)-based vectors offer a promising system for delivery and expression of full-length human genes any size. HACs avoid the limited cloning capacity, lack copy number control, insertional mutagenesis caused by integration into host chromosomes that plague viral vectors. We previously described synthetic HAC can be easily eliminated from cell populations inactivation its conditional kinetochore. Here, we demonstrate utility this HAC, which has unique gene acceptor...

The cytoskeleton plays an important role in neuronal morphogenesis. We have identified and characterized a novel actin-binding protein, termed Mayven, predominantly expressed brain. Mayven contains BTB (broad complex, tramtrack, bric-a-brac)/POZ (poxvirus, zinc finger) domain-like structure the predicted N terminus “kelch repeats” C-terminal domain. shares 63% identity (77% similarity) with Drosophila ring canal (“kelch”) protein. Somatic cell-hybrid analysis indicated that human gene is...

Smad3, a major intracellular mediator of TGFβ signaling, functions as both positive and negative regulator in carcinogenesis. In response to TGFβ, the receptor phosphorylates serine residues at Smad3 C-tail. Cancer cells often contain high levels MAPK CDK activities, which can lead linker region becoming highly phosphorylated. Here, we report, for first time, that mutation phosphorylation sites markedly inhibited primary tumor growth, but significantly increased lung metastasis breast cancer...

Abstract Rearrangement of the cytoskeleton leading to extension cellular processes is essential for myelination axons by oligodendrocytes. We observed that actin‐binding protein, Mayven, expressed during all stages oligodendrocyte lineage, and its expression up‐regulated differentiation. Mayven localized in cytoplasm along cell processes. also binds actin, involved cytoskeletal reorganization precursor cells (O‐2A cells) leads process elongation. overexpression resulted an increase outgrowth...

Abstract: Glutamate is the major excitatory neurotransmitter in CNS. Although its role neurons has been studied extensively, little known about function astrocytes. We effects of glutamate on signaling pathways primary found that tyrosine kinase related adhesion focal (RAFTK) phosphorylated response to a time‐ and dose‐dependent manner. This phosphorylation was pertussis toxin (PTX) sensitive could be attenuated by depletion Ca 2+ from intracellular stores. RAFTK mediated primarily class...

The neuronal nuclear matrix protein, NRP/B, contains a BTB domain and kelch repeats is expressed in primary neurons but not glial cells. To examine the function of NRP/B neurons, we analyzed structure/function NRP/B-BTB its role neurite outgrowth. Based on three-dimensional modeling generated an mutant containing three mutations conserved amino acids D47A, H60A R61D that was termed A. A significantly reduced dimerization compared to wild-type NRP/B. required for localization mediated...

NRP/B, a family member of the BTB/Kelch repeat proteins, is implicated in neuronal and cancer development, as well regulation oxidative stress responses breast brain cancer. Our previous studies indicate that NRP/B-BTB/POZ domain involved dimerization NRP/B complex formation with tumor suppressor, retinoblastoma protein. Although much evidence supports potential role molecular mechanisms action on E2F transcription factors have not been elucidated.Three-dimensional modeling was used to...

Abstract The mechanism by which transforming growth factor beta (TGFβ) exerts stimulatory effects was examined in C3H/10T1/2 mouse fibroblasts study of cell cycle regulation the retinoblastoma gene product (p110 Rb ) and transcriptional p110 ‐associated transcription factor, E2F. Northern blotting analysis shows that TGFβ and/or epidermal (EGF) stimulate three to sixfold level mRNA is also reflected increased levels . becomes phosphorylated mid‐G1 further at G 1 /S transition....

In most of human cancer, the c-Myc proto-oncogene is highly activated. Dysregulation oncoprotein contributes to drive tumorigenesis in numerous tissues and organs. Thus, targeting stability can be a critical step for cancer therapy. Here we report Smad7 as key molecule regulate activity by recruiting F-box protein, Skp2. Ectopic expression down-regulated protein level without affecting transcription significantly repressed its transcriptional activity, leading inhibition cell proliferation...

A concise and scalable synthetic route for optically pure (4S) (4R)-5-(3′,4′-dihydroxyphenyl)-γ-valerolactones (DHPVs), catechin metabolites, has been developed via the efficient construction of a γ-valerolactone moiety from hexenol. Noticeably, different skin wrinkle-reducing activities each metabolite were revealed our unique syntheses DHPVs in an enantiomerically form.

Gastrointestinal cancer is associated with a high mortality rate. Here, we report that the splice variant of NRP/B contributes to tumorigenic activity in highly malignant gastric through dissociation from tumor repressor, HDAC5. mRNA expression significantly higher human tissues than normal tissues. Further, levels both and Lgr5, but not full-length protein, are found cells, non-tumorigenic cells. The loss markedly inhibits cell migration invasion, which reduces formation vivo. Importantly,...

Abstract In most of human cancer, the c-Myc proto-oncogene is highly activated. Dysregulation oncoprotein contributes to drive tumorigenesis in numerous tissues and organs. Thus, targeting stability can be a critical step for cancer therapy. Here we report Smad7 as key molecule regulate activity by recruiting F-box protein, Skp2. Ectopic expression down-regulated protein level without affecting transcription significantly repressed its transcriptional activity, leading inhibition cell...

<div>Abstract<p>Smad3, a major intracellular mediator of TGFβ signaling, functions as both positive and negative regulator in carcinogenesis. In response to TGFβ, the receptor phosphorylates serine residues at Smad3 C-tail. Cancer cells often contain high levels MAPK CDK activities, which can lead linker region becoming highly phosphorylated. Here, we report, for first time, that mutation phosphorylation sites markedly inhibited primary tumor growth, but significantly increased...

<p>Supplemental Figures 1-5 and Supplemental Methods. Supplementary Figure 1. Blockade of Smad3 phosphorylation at the C-terminal linker region by infection with adenoviral mutants. 2. Mutation sites enhances TGF-β1-induced growth arrest apoptosis. 3. suppresses transcriptional activity. 4. promotes TGF-β-induced EMT invasive 5. significantly inhibits expression embryonic transcription factors, mammosphere formation, colony formation on soft agar.</p>

<p>Supplemental Figures 1-5 and Supplemental Methods. Supplementary Figure 1. Blockade of Smad3 phosphorylation at the C-terminal linker region by infection with adenoviral mutants. 2. Mutation sites enhances TGF-β1-induced growth arrest apoptosis. 3. suppresses transcriptional activity. 4. promotes TGF-β-induced EMT invasive 5. significantly inhibits expression embryonic transcription factors, mammosphere formation, colony formation on soft agar.</p>

<div>Abstract<p>Smad3, a major intracellular mediator of TGFβ signaling, functions as both positive and negative regulator in carcinogenesis. In response to TGFβ, the receptor phosphorylates serine residues at Smad3 C-tail. Cancer cells often contain high levels MAPK CDK activities, which can lead linker region becoming highly phosphorylated. Here, we report, for first time, that mutation phosphorylation sites markedly inhibited primary tumor growth, but significantly increased...

Abstract Human artificial chromosome (HAC)-based vectors offer a promising system for delivery and expression of full-length human genes any size. Due to their unique maintenance features unlimited cloning capacity, HACs avoid the lack copy number control insertional mutagenesis caused by integration into host chromosomes that plague viral vectors. We previously described synthetic HAC can be easily eliminated from cell populations inactivation its conditional kinetochore. Here, we...

Abstract Myc, a pleiotropic transcription factor, plays prominent role in human cancer progression. The regulation of Myc stability, therefore, is critical to understand the molecular mechanism tumorigenesis various cancers. stability tightly regulated by activity ubiqutin ligases, Skp2 and Fbw7. However, key mediator this process has not been addressed yet. Here, we have identified Smad7 as an intermediary regulating recruiting F-box protein, Skp2. Microarray analysis using cell lines...