TID1, a human homolog of the Drosophila tumor suppressor l(2)tid, encodes two mitochondrial modulators of apoptosis with opposing functions.
AuthorsSyken J, De-Medina T, Munger K
JournalProc Natl Acad Sci U S A
PubMed ID10411904
'Mitochondria have emerged as central regulators of apoptosis. Here, we show that TID1, a human homolog of the Drosophila tumor suppressor lethal (2) tumorous imaginal discs, l(2)tid, encodes two mitochondrial matrix proteins, designated hTid-1(L) and hTid-1(S). These splice variants are both highly conserved members of the DnaJ family of proteins, ... More
Presenilin 1 mutations activate gamma 42-secretase but reciprocally inhibit epsilon-secretase cleavage of amyloid precursor protein (APP) and S3-cleavage of notch.
Authors Chen Fusheng; Gu YongJun; Hasegawa Hiroshi; Ruan Xueying; Arawaka Shigeki; Fraser Paul; Westaway David; Mount Howard; St George-Hyslop Peter;
JournalJ Biol Chem
PubMed ID12119298
'The presenilin 1 (PS1) and presenilin 2 (PS2) proteins are necessary for proteolytic cleavage of the amyloid precursor protein (APP) within its transmembrane domain. One of these cleavage events (termed gamma-secretase) generates the C-terminal end of the Abeta-peptide by proteolysis near residue 710 or 712 of APP(770). Another event (termed ... More
Pattern of genes influenced by conditional expression of the transcription factors HNF6, HNF4alpha and HNF1beta in a pancreatic beta-cell line.
'Using the rat insulinoma cell line INS-1 we generated beta-cell clones that are most efficient for gene transfer, as they contain an FRT site for Flp recombinase-mediated, site-directed integration of a single copy transgene. Therefore, the gene-of-interest can be introduced by DNA transfection without the need to select individual cell ... More
Protein tyrosine phosphatase-PEST regulates focal adhesion disassembly, migration, and cytokinesis in fibroblasts.
AuthorsAngers-Loustau A, Cote JF, Charest A, Dowbenko D, Spencer S, Lasky LA, Tremblay ML
JournalJ Cell Biol
PubMed ID10085298
'In this article, we show that, in transfected COS-1 cells, protein tyrosine phosphatase (PTP)-PEST translocates to the membrane periphery following stimulation by the extracellular matrix protein fibronectin. When plated on fibronectin, PTP-PEST (-/-) fibroblasts display a strong defect in motility. 3 h after plating on fibronectin, the number and size ... More
Human immunodeficiency virus type 1 Vpr-dependent cell cycle arrest through a mitogen-activated protein kinase signal transduction pathway.
AuthorsYoshizuka N, Yoshizuka-Chadani Y, Krishnan V, Zeichner SL,
JournalJ Virol
PubMed ID16103188
The human immunodeficiency virus type 1 (HIV-1) Vpr protein has important functions in advancing HIV pathogenesis via several effects on the host cell. Vpr mediates nuclear import of the preintegration complex, induces host cell apoptosis, and inhibits cell cycle progression at G(2), which increases HIV gene expression. Some of Vpr's ... More
Endocytic function, glycosaminoglycan specificity, and antibody sensitivity of the recombinant human 190-kDa hyaluronan receptor for endocytosis (HARE).
AuthorsHarris EN, Weigel JA, Weigel PH,
JournalJ Biol Chem
PubMed ID15208308
The human hyaluronan receptor for endocytosis (hHARE) mediates the endocytic clearance of hyaluronan (HA) and chondroitin sulfate from lymph fluid and blood. Two hHARE isoforms (190 and 315 kDa) are present in sinusoidal endothelial cells of liver, spleen, and lymph nodes (Zhou, B., McGary, C. T., Weigel, J. A., Saxena, ... More
Mevalonate kinase is a cytosolic enzyme in humans.
In the past decade several reports have appeared which suggest that peroxisomes play a central role in isoprenoid/cholesterol biosynthesis. These suggestions were based primarily on the reported finding of several of the enzymes of the presqualene segment of the biosynthetic pathway in peroxisomes. More recently, however, conflicting results have been ... More
Ca2+-dependent potentiation of the nonselective cation channel TRPV4 is mediated by a C-terminal calmodulin binding site.
AuthorsStrotmann R, Schultz G, Plant TD,
JournalJ Biol Chem
PubMed ID12724311
Most Ca2+-permeable ion channels are inhibited by increases in the intracellular Ca2+ concentration ([Ca2+]i), thus preventing potentially deleterious rises in [Ca2+]i. In this study, we demonstrate that currents through the osmo-, heat- and phorbol ester-sensitive, Ca2+-permeable nonselective cation channel TRPV4 are potentiated by intracellular Ca2+. Spontaneous TRPV4 currents and currents ... More
Hematopoietic activity of a stromal cell transmembrane protein containing epidermal growth factor-like repeat motifs.
AuthorsMoore KA, Pytowski B, Witte L, Hicklin D, Lemischka IR
JournalProc Natl Acad Sci U S A
PubMed ID9108096
Primitive hematopoietic stem cells are closely associated with discrete in vivo microenvironments. These niches are thought to provide the molecular signals that mediate stem cell differentiation and self- renewal. We have dissected the fetal liver microenvironment into distinct cellular components by establishing an extensive panel of stromal cell lines. One ... More
The C terminus of Ku80 activates the DNA-dependent protein kinase catalytic subunit.
AuthorsSingleton BK, Torres-Arzayus MI, Rottinghaus ST, Taccioli GE, Jeggo PA
JournalMol Cell Biol
PubMed ID10207052
Ku is a heterodimeric protein with double-stranded DNA end-binding activity that operates in the process of nonhomologous end joining. Ku is thought to target the DNA-dependent protein kinase (DNA-PK) complex to the DNA and, when DNA bound, can interact and activate the DNA-PK catalytic subunit (DNA-PKcs). We have carried out ... More
Bilirubin, formed by activation of heme oxygenase-2, protects neurons against oxidative stress injury.
AuthorsDore S, Takahashi M, Ferris CD, Hester LD, Guastella D, Snyder SH
JournalProc Natl Acad Sci U S A
PubMed ID10051662
Heme oxygenase (HO) catalyzes the conversion of heme to carbon monoxide, iron, and biliverdin, which is immediately reduced to bilirubin (BR). Two HO active isozymes exist: HO1, an inducible heat shock protein, and HO2, which is constitutive and highly concentrated in neurons. We demonstrate a neuroprotective role for BR formed ... More
Forkhead family transcription factor FKHRL1 is expressed in human megakaryocytes. Regulation of cell cycling as a downstream molecule of thrombopoietin signaling.
AuthorsTanaka M, Kirito K, Kashii Y, Uchida M, Watanabe T, Endo H, Endoh T, Sawada K, Ozawa K, Komatsu N,
JournalJ Biol Chem
PubMed ID11278373
FKHRL1, a member of the Forkhead transcription factor family, is one of the downstream molecules of phosphatidylinositol 3-kinase-Akt. This molecule is a mammalian homolog of DAF-16, which plays an important role in the longevity of Caenorhabditis elegans. In this study we found that Akt and FKHRL1 proteins were detectable in ... More
Growth inhibition by keratinocyte growth factor receptor of human salivary adenocarcinoma cells through induction of differentiation and apoptosis.
Authors Zhang Y; Wang H; Toratani S; Sato J D; Kan M; McKeehan W L; Okamoto T;
JournalProc Natl Acad Sci U S A
PubMed ID11562460
We have reported that normal human salivary gland-derived epithelial cells exclusively express keratinocyte growth factor receptor (KGFR). In the process of malignant transformation of human salivary gland tumors, KGFR gene expression disappeared concomitantly with the de novo expression of the fibroblast growth factor receptor 1 (FGFR1) and FGFR4 genes. In ... More
ZUFSP Deubiquitylates K63-Linked Polyubiquitin Chains to Promote Genome Stability.
AuthorsHaahr P, Borgermann N, Guo X, Typas D, Achuthankutty D, Hoffmann S, Shearer R, Sixma TK, Mailand N,
JournalMol Cell
PubMed ID29576528
'Deubiquitylating enzymes (DUBs) enhance the dynamics of the versatile ubiquitin (Ub) code by reversing and regulating cellular ubiquitylation processes at multiple levels. Here we discovered that the uncharacterized human protein ZUFSP (zinc finger with UFM1-specific peptidase domain protein/C6orf113/ZUP1), which has been annotated as a potentially inactive UFM1 protease, and its ... More
Culture and establishment of self-renewing human and mouse adult liver and pancreas 3D organoids and their genetic manipulation.
AuthorsBroutier L, Andersson-Rolf A, Hindley CJ, Boj SF, Clevers H, Koo BK, Huch M
JournalNat Protoc
PubMed ID27560176
Adult somatic tissues have proven difficult to expand in vitro, largely because of the complexity of recreating appropriate environmental signals in culture. We have overcome this problem recently and developed culture conditions for adult stem cells that allow the long-term expansion of adult primary tissues from small intestine, stomach, liver ... More
A novel derivative of the fungal antimicrobial peptide plectasin is active against Mycobacterium tuberculosis.
AuthorsTenland E, Krishnan N, Rönnholm A, Kalsum S, Puthia M, Mörgelin M, Davoudi M, Otrocka M, Alaridah N, Glegola-Madejska I, Sturegård E, Schmidtchen A, Lerm M, Robertson BD, Godaly G
JournalTuberculosis (Edinb)
PubMed ID30514507
Tuberculosis has been reaffirmed as the infectious disease causing most deaths in the world. Co-infection with HIV and the increase in multi-drug resistant Mycobacterium tuberculosis strains complicate treatment and increases mortality rates, making the development of new drugs an urgent priority. In this study we have identified a promising candidate ... More
YKL-40/CHI3L1 facilitates migration and invasion in HER2 overexpressing breast epithelial progenitor cells and generates a niche for capillary-like network formation.
AuthorsMorera E, Steinhäuser SS, Budkova Z, Ingthorsson S, Kricker J, Krueger A, Traustadottir GA, Gudjonsson T
JournalIn Vitro Cell Dev Biol Anim
PubMed ID31482369
Epithelial to mesenchymal transition (EMT) is a developmental event that is hijacked in some diseases such as fibrosis and cancer. In cancer, EMT has been linked to increased invasion and metastasis and is generally associated with a poor prognosis. In this study, we have compared phenotypic and functional differences between ... More
A fully human transgene switch to regulate therapeutic protein production by cooling sensation.
AuthorsBai P, Liu Y, Xue S, Hamri GC, Saxena P, Ye H, Xie M, Fussenegger M
JournalNat Med
PubMed ID31285633
The ability to safely control transgene expression with simple synthetic gene switches is critical for effective gene- and cell-based therapies. In the present study, the signaling pathway controlled by human transient receptor potential (TRP) melastatin 8 (hTRPM8), a TRP channel family member ... More