A high-throughput, cell-based screening method for siRNA and small molecule inhibitors of mTORC1 signaling using the In Cell Western technique.
AuthorsHoffman GR, Moerke NJ, Hsia M, Shamu CE, Blenis J,
JournalAssay Drug Dev Technol
PubMed ID20085456
'The mTORC1 pathway is a central regulator of cell growth, and defective mTORC1 regulation plays a causative role in a variety of human diseases, including cancer, tumor syndromes such as the tuberous sclerosis complex (TSC) and lymphangioleiomyomatosis (LAM), and metabolic diseases such as diabetes and obesity. Given the importance of ... More
Processing of Pro-atrial Natriuretic Peptide by Corin in Cardiac Myocytes.
Authors Wu Faye; Yan Wei; Pan Junliang; Morser John; Wu Qingyu;
JournalJ Biol Chem
PubMed ID11884416
'Corin is a type II transmembrane serine protease abundantly expressed in the heart. In a previous study using transfected 293 cells, we showed that corin converted pro-atrial natriuretic peptide (pro-ANP) to atrial natriuretic peptide (ANP), suggesting that corin is likely the pro-ANP convertase. Because other serine proteases such as thrombin ... More
Systems survey of endocytosis by multiparametric image analysis.
AuthorsCollinet C, Stöter M, Bradshaw CR, Samusik N, Rink JC, Kenski D, Habermann B, Buchholz F, Henschel R, Mueller MS, Nagel WE, Fava E, Kalaidzidis Y, Zerial M,
JournalNature
PubMed ID20190736
'Endocytosis is a complex process fulfilling many cellular and developmental functions. Understanding how it is regulated and integrated with other cellular processes requires a comprehensive analysis of its molecular constituents and general design principles. Here, we developed a new strategy to phenotypically profile the human genome with respect to transferrin ... More
N-glycans are direct determinants of CFTR folding and stability in secretory and endocytic membrane traffic.
'N-glycosylation, a common cotranslational modification, is thought to be critical for plasma membrane expression of glycoproteins by enhancing protein folding, trafficking, and stability through targeting them to the ER folding cycles via lectin-like chaperones. In this study, we show that N-glycans, specifically core glycans, enhance the productive folding and conformational ... More
Disinhibition of neurotrophin-induced dorsal root ganglion cell neurite outgrowth on CNS myelin by siRNA-mediated knockdown of NgR, p75(NTR) and Rho-A.
AuthorsAhmed Z, Dent RG, Suggate EL, Barrett LB, Seabright RJ, Berry M, Logan A,
JournalMol Cell Neurosci
PubMed ID15737741
'The presence of multiple axon growth inhibitors may partly explain why central nervous system axons are generally incapable of regenerating after injury. Using RNA interference (RNAi) in dorsal root ganglia neurons (DRGN), we demonstrate siRNA-mediated silencing of components of the inhibitory signalling cascade, including p75(NTR), NgR and Rho-A mRNA, of ... More
M phase phosphoprotein 1 is a human plus-end-directed kinesin-related protein required for cytokinesis.
AuthorsAbaza A, Soleilhac JM, Westendorf J, Piel M, Crevel I, Roux A, Pirollet F,
JournalJ Biol Chem
PubMed ID12740395
'The human M phase phosphoprotein 1 (MPP1), previously identified through a screening of a subset of proteins specifically phosphorylated at the G2/M transition (Matsumoto-Taniura, N., Pirollet, F., Monroe, R., Gerace, L., and Westendorf, J. M. (1996) Mol. Biol. Cell 7, 1455-1469), is characterized as a plus-end-directed kinesin-related protein. Recombinant MPP1 ... More
Repression of Na,K-ATPase beta1-subunit by the transcription factor snail in carcinoma.
AuthorsEspineda CE, Chang JH, Twiss J, Rajasekaran SA, Rajasekaran AK,
JournalMol Biol Cell
PubMed ID14699059
'The Na,K-ATPase consists of two essential alpha- and beta-subunits and regulates the intracellular Na+ and K+ homeostasis. Although the alpha-subunit contains the catalytic activity, it is not active without functional beta-subunit. Here, we report that poorly differentiated carcinoma cell lines derived from colon, breast, kidney, and pancreas show reduced expression ... More
Regulation of peroxiredoxin I activity by Cdc2-mediated phosphorylation.
Authors Chang Tong-Shin; Jeong Woojin; Choi Soon Young; Yu Shiqin; Kang Sang Won; Rhee Sue Goo;
JournalJ Biol Chem
PubMed ID11986303
'Hydrogen peroxide is implicated as an intracellular messenger in various cellular responses such as proliferation and differentiation. Peroxiredoxin (Prx) I is a member of the peroxiredoxin family of peroxidases and contains a consensus site (Thr(90)-Pro-Lys-Lys) for phosphorylation by cyclin-dependent kinases (CDKs). This protein has now been shown to be phosphorylated ... More
A role of the C-terminal region of human Rad9 (hRad9) in nuclear transport of the hRad9 checkpoint complex.
Authors Hirai Itaru; Wang Hong-Gang;
JournalJ Biol Chem
PubMed ID11994305
'Rad9, Rad1, and Hus1 are members of the Rad family of checkpoint proteins that are required for both DNA replication and DNA damage checkpoints and are thought to function as sensors in the DNA integrity checkpoint control. These proteins can interact with each other and form a stable proliferating cell ... More
TGF-beta-induced RhoA and p160ROCK activation is involved in the inhibition of Cdc25A with resultant cell-cycle arrest.
AuthorsBhowmick NA, Ghiassi M, Aakre M, Brown K, Singh V, Moses HL,
JournalProc Natl Acad Sci U S A
PubMed ID14657354
'The ability of the transforming growth factor beta (TGF-beta) signaling pathways to inhibit proliferation of most cells while stimulating proliferation of others remains a conundrum. In this article, we report that the absence of RhoA and p160ROCK activity in fibroblastic NIH 3T3 cells and its presence in epithelial NMuMG cells ... More
Surface Calreticulin Mediates Muramyl Dipeptide-induced Apoptosis in RK13 Cells.
'Calreticulin (CRT) is a binding protein for apoptotic N-acetylmuramyl-l-alanyl-d-isoglutamine (l,d-MDP) or peptidoglycan in RK(13) cells. CRT on RK(13) cell surface (srCRT) forms complex(es) with tumor necrosis factor receptor 1 (TNFR1) and TNFR-associated death domain (TRADD) protein of the cell membrane. CRT polyclonal or monoclonal antibody binding to RK(13) srCRT dose-dependently ... More
Roles of TRP14, a thioredoxin-related protein in tumor necrosis factor-alpha signaling pathways.
AuthorsJeong W, Chang TS, Boja ES, Fales HM, Rhee SG,
JournalJ Biol Chem
PubMed ID14607843
'The possible roles of a 14-kDa human thioredoxin (Trx)-related protein (TRP14) in TNF-alpha signaling were studied in comparison with those of Trx1 by RNA interference in HeLa cells. Depletion of TRP14 augmented the TNF-alpha-induced phosphorylation and degradation of I kappa B alpha as well as the consequent activation of NF-kappa ... More
Identification of essential genes in cultured mammalian cells using small interfering RNAs.
Authors Harborth J; Elbashir S M; Bechert K; Tuschl T; Weber K;
JournalJ Cell Sci
PubMed ID11792820
'We report the first RNAi-induced phenotypes in mammalian cultured cells using RNA interference mediated by duplexes of 21-nt RNAs. The 21 gene products studied have different functions and subcellular localizations. Knockdown experiments monitored by immunofluorescence and immunoblotting show that even major cellular proteins such as actin and vimentin can be ... More
The circadian regulatory proteins BMAL1 and cryptochromes are substrates of casein kinase Iepsilon.
Authors Eide Erik J; Vielhaber Erica L; Hinz William A; Virshup David M;
JournalJ Biol Chem
PubMed ID11875063
'The serine/threonine protein kinase casein kinase I epsilon (CKIepsilon) is a key regulator of metazoan circadian rhythm. Genetic and biochemical data suggest that CKIepsilon binds to and phosphorylates the PERIOD proteins. However, the PERIOD proteins interact with a variety of circadian regulators, suggesting the possibility that CKIepsilon may interact with ... More
Antibody mediated in vivo delivery of small interfering RNAs via cell-surface receptors.
AuthorsSong E, Zhu P, Lee SK, Chowdhury D, Kussman S, Dykxhoorn DM, Feng Y, Palliser D, Weiner DB, Shankar P, Marasco WA, Lieberman J,
JournalNat Biotechnol
PubMed ID15908939
'Delivery of small interfering RNAs (siRNAs) into cells is a key obstacle to their therapeutic application. We designed a protamine-antibody fusion protein to deliver siRNA to HIV-infected or envelope-transfected cells. The fusion protein (F105-P) was designed with the protamine coding sequence linked to the C terminus of the heavy chain ... More
ATR regulates fragile site stability.
AuthorsCasper AM, Nghiem P, Arlt MF, Glover TW,
JournalCell
PubMed ID12526805
'Conditions that partially inhibit DNA replication induce expression of common fragile sites. These sites form gaps and breaks on metaphase chromosomes and are deleted and rearranged in many tumors. Yet, the mechanism of fragile site expression has been elusive. We demonstrate that the replication checkpoint kinase ATR, but not ATM, ... More
Mitochondrial autophagy is an HIF-1-dependent adaptive metabolic response to hypoxia.
AuthorsZhang H, Bosch-Marce M, Shimoda LA, Tan YS, Baek JH, Wesley JB, Gonzalez FJ, Semenza GL,
JournalJ Biol Chem
PubMed ID18281291
Autophagy is a process by which cytoplasmic organelles can be catabolized either to remove defective structures or as a means of providing macromolecules for energy generation under conditions of nutrient starvation. In this study we demonstrate that mitochondrial autophagy is induced by hypoxia, that this process requires the hypoxia-dependent factor-1-dependent ... More
CARF is a novel protein that cooperates with mouse p19ARF (human p14ARF) in activating p53.
Authors Hasan Md Kamrul; Yaguchi Tomoko; Sugihara Takashi; Kumar Penmetcha K R; Taira Kazunari; Reddel Roger R; Kaul Sunil C; Wadhwa Renu;
JournalJ Biol Chem
PubMed ID12154087
The INK4a locus on chromosome 9p21 encodes two structurally distinct tumor suppressor proteins, p16(INK4a) and the alternative reading frame protein, ARF (p19(ARF) in mouse and p14(ARF) in human). Each of these proteins has a role in senescence of primary cells and activates pathways for cell cycle control and tumor suppression. ... More
E2F4/5 and p107 as Smad cofactors linking the TGFbeta receptor to c-myc repression.
Smad3 is a direct mediator of transcriptional activation by the TGFbeta receptor. Its target genes in epithelial cells include cyclin-dependent kinase inhibitors that generate a cytostatic reponse. We defined how, in the same context, Smad3 can also mediate transcriptional repression of the growth-promoting gene c-myc. A complex containing Smad3, the ... More
The beta-catenin/TCF-4 complex imposes a crypt progenitor phenotype on colorectal cancer cells.
Authors van de Wetering Marc; Sancho Elena; Verweij Cornelis; de Lau Wim; Oving Irma; Hurlstone Adam; van der Horn Karin; Batlle Eduard; Coudreuse Damien; Haramis Anna Pavlina; Tjon-Pon-Fong Menno; Moerer Petra; van den Born Maaike; Soete Gwen; Pals Steven; Eilers Martin; Medema Rene; Clevers Hans;
JournalCell
PubMed ID12408868
The transactivation of TCF target genes induced by Wnt pathway mutations constitutes the primary transforming event in colorectal cancer (CRC). We show that disruption of beta-catenin/TCF-4 activity in CRC cells induces a rapid G1 arrest and blocks a genetic program that is physiologically active in the proliferative compartment of colon ... More
Presenilin Couples the Paired Phosphorylation of beta-Catenin Independent of Axin. Implications for beta-Catenin Activation in Tumorigenesis.
Authors Kang David; Soriano Salvador; Xia Xuefeng; Eberhart Charles; De Strooper Bart; Zheng Hui; Koo Edward;
JournalCell
PubMed ID12297048
The Alzheimer's disease-linked gene presenilin 1 (PS1) is required for intramembrane proteolysis of APP and Notch. In addition, recent observations strongly implicate PS1 as a negative regulator of the Wnt/beta-catenin signaling pathway, although the mechanism underlying this activity is unknown. Here, we show that presenilin functions as a scaffold that ... More
Raptor, a binding partner of target of rapamycin (TOR), mediates TOR action.
mTOR controls cell growth, in part by regulating p70 S6 kinase alpha (p70alpha) and eukaryotic initiation factor 4E binding protein 1 (4EBP1). Raptor is a 150 kDa mTOR binding protein that also binds 4EBP1 and p70alpha. The binding of raptor to mTOR is necessary for the mTOR-catalyzed phosphorylation of 4EBP1 ... More
Induction of androgen receptor-dependent apoptosis in prostate cancer cells by the retinoblastoma protein.
AuthorsWang X, Deng H, Basu I, Zhu L,
JournalCancer Res
PubMed ID14973061
Re-expression of a tumor suppressor in tumor cells that lack it is an effective way to study its functional activities. However, because tumor cells contain multiple mutations, tumor suppressor functions that are dependent on (an)other regulators are unlikely to be identified by its re-expression alone if the other regulators are ... More
A novel human nucleolar protein, Nop132, binds to the G proteins, RRAG A/C/D.
AuthorsSekiguchi T, Todaka Y, Wang Y, Hirose E, Nakashima N, Nishimoto T,
JournalJ Biol Chem
PubMed ID14660641
RRAG A (Rag A)/Gtr1p is a member of the Ras-like small G protein family that genetically interacts with RCC1, a guanine nucleotide exchange factor for RanGTPase. RRAG A/Gtr1p forms a heterodimer with other G proteins, RRAG C and RRAG D/Gtr2p, in a nucleotide-independent manner. To further elucidate the function of ... More
Cerebellar long-term synaptic depression requires PKC-mediated activation of CPI-17, a myosin/moesin phosphatase inhibitor.
AuthorsEto M, Bock R, Brautigan DL, Linden DJ,
JournalNeuron
PubMed ID12495628
Cerebellar LTD requires brief activation of PKC and is expressed as a functional downregulation of AMPA receptors. Modulation of vascular smooth-muscle contraction by G protein-coupled receptors (called Ca(2+) sensitization) also involves PKC phosphorylation and activation of a specific inhibitor of myosin/moesin phosphatase (MMP). This inhibitor, called CPI-17, is also expressed ... More
Functional studies of the PI(3)-kinase signalling pathway employing synthetic and expressed siRNA.
AuthorsCzauderna F, Fechtner M, Aygün H, Arnold W, Klippel A, Giese K, Kaufmann J,
JournalNucleic Acids Res
PubMed ID12527776
RNA interference (RNAi) is a RNA-mediated sequence-specific gene silencing mechanism. Recently, this mechanism has been used to down-regulate protein expression in mammalian cells by applying synthetic- or vector-generated small interfering RNAs (siRNAs). However, for the evaluation of this new knockdown technology, it is crucial to demonstrate biological consequences beyond protein ... More
Concurrent versus individual binding of HuR and AUF1 to common labile target mRNAs.
AuthorsLal A, Mazan-Mamczarz K, Kawai T, Yang X, Martindale JL, Gorospe M,
JournalEMBO J
PubMed ID15257295
RNA-binding proteins HuR and AUF1 bind to many common AU-rich target mRNAs and exert opposing influence on target mRNA stability, but the functional interactions between HuR and AUF1 have not been systematically studied. Here, using common target RNAs encoding p21 and cyclin D1, we provide evidence that HuR and AUF1 ... More
The Cell Cycle-regulated Protein Human GTSE-1 Controls DNA Damage-induced Apoptosis by Affecting p53 Function.
AuthorsMonte M, Benetti R, Buscemi G, Sandy P, Del Sal G, Schneider C,
JournalJ Biol Chem
PubMed ID12750368
GTSE-1 (G2 and S phase-expressed-1) protein is specifically expressed during S and G2 phases of the cell cycle. It is mainly localized to the microtubules and when overexpressed delays the G2 to M transition. Here we report that human GTSE-1 (hGTSE-1) protein can negatively regulate p53 transactivation function, protein levels, ... More
Suppression of apoptosis by cyclophilin D via stabilization of hexokinase II mitochondrial binding in cancer cells.
AuthorsMachida K, Ohta Y, Osada H,
JournalJ Biol Chem
PubMed ID16551620
The permeability transition pore is involved in the mitochondrial pathway of apoptosis. Cyclophilin D, a pore component, has catalytic activity as a peptidyl prolyl cis, trans-isomerase (PPIase), which is essential to the pore opening. It has been reported that cyclophilin D overexpression suppresses apoptosis in cancer cells. To clarify the ... More
The Nck-interacting kinase phosphorylates ERM proteins for formation of lamellipodium by growth factors.
AuthorsBaumgartner M, Sillman AL, Blackwood EM, Srivastava J, Madson N, Schilling JW, Wright JH, Barber DL,
JournalProc Natl Acad Sci U S A
PubMed ID16938849
The mammalian Ste20-like Nck-interacting kinase (NIK) and its orthologs Misshapen in Drosophila and Mig-15 in Caenorhabditis elegans have a conserved function in regulating cell morphology, although through poorly understood mechanisms. We report two previously unrecognized actions of NIK: regulation of lamellipodium formation by growth factors and phosphorylation of the ERM ... More
The mitochondrial protein hFis1 regulates mitochondrial fission in mammalian cells through an interaction with the dynamin-like protein DLP1.
AuthorsYoon Y, Krueger EW, Oswald BJ, McNiven MA,
JournalMol Cell Biol
PubMed ID12861026
The yeast protein Fis1p has been shown to participate in mitochondrial fission mediated by the dynamin-related protein Dnm1p. In mammalian cells, the dynamin-like protein DLP1/Drp1 functions as a mitochondrial fission protein, but the mechanisms by which DLP1/Drp1 and the mitochondrial membrane interact during the fission process are undefined. In this ... More
ZRP-1 controls Rho GTPase-mediated actin reorganization by localizing at cell-matrix and cell-cell adhesions.
AuthorsBai CY, Ohsugi M, Abe Y, Yamamoto T,
JournalJ Cell Sci
PubMed ID17652164
Focal adhesion protein ZRP-1/TRIP6 has been implicated in actin reorganization and cell motility. The role of ZRP-1, however, remained obscure because previously reported data are often conflicting one another. In the present study, we examined roles of ZRP-1 in HeLa cells. ZRP-1 is localized to the cell-cell contact sites as ... More
A structural basis for discriminating between self and nonself double-stranded RNAs in mammalian cells.
AuthorsMarques JT, Devosse T, Wang D, Zamanian-Daryoush M, Serbinowski P, Hartmann R, Fujita T, Behlke MA, Williams BR,
JournalNat Biotechnol
PubMed ID16648842
Nonspecific effects triggered by small interfering RNAs (siRNAs) complicate the use of RNA interference (RNAi) to specifically downregulate gene expression. To uncover the basis of these nonspecific activities, we analyzed the effect of chemically synthesized siRNAs on mammalian double-stranded RNA (dsRNA)-activated signaling pathways. siRNAs ranging from 21 to 27 nucleotides ... More
Triggered release of siRNA from poly(ethylene glycol)-protected, pH-dependent liposomes.
AuthorsAuguste DT, Furman K, Wong A, Fuller J, Armes SP, Deming TJ, Langer R,
JournalJ Control Release
PubMed ID18601962
The ability of small interfering RNA (siRNA) to regulate gene expression has potential therapeutic applications, but its use is limited by inefficient delivery. Triggered release of adsorbed poly(ethylene glycol) (PEG)-b-polycation polymers from pH-dependent (PD) liposomes enables protection from immune recognition during circulation (pH 7.4) and subsequent intracellular delivery of siRNA ... More
Early endosomes and endosomal coatomer are required for autophagy.
AuthorsRazi M, Chan EY, Tooze SA,
JournalJ Cell Biol
PubMed ID19364919
Autophagy, an intracellular degradative pathway, maintains cell homeostasis under normal and stress conditions. Nascent double-membrane autophagosomes sequester and enclose cytosolic components and organelles, and subsequently fuse with the endosomal pathway allowing content degradation. Autophagy requires fusion of autophagosomes with late endosomes, but it is not known if fusion with early ... More
Angiogenesis selectively requires the p110alpha isoform of PI3K to control endothelial cell migration.
AuthorsGraupera M, Guillermet-Guibert J, Foukas LC, Phng LK, Cain RJ, Salpekar A, Pearce W, Meek S, Millan J, Cutillas PR, Smith AJ, Ridley AJ, Ruhrberg C, Gerhardt H, Vanhaesebroeck B,
JournalNature
PubMed ID18449193
Phosphoinositide 3-kinases (PI3Ks) signal downstream of multiple cell-surface receptor types. Class IA PI3K isoforms couple to tyrosine kinases and consist of a p110 catalytic subunit (p110alpha, p110beta or p110delta), constitutively bound to one of five distinct p85 regulatory subunits. PI3Ks have been implicated in angiogenesis, but little is known about ... More
Therapeutic suppression of translation initiation factor eIF4E expression reduces tumor growth without toxicity.
AuthorsGraff JR, Konicek BW, Vincent TM, Lynch RL, Monteith D, Weir SN, Schwier P, Capen A, Goode RL, Dowless MS, Chen Y, Zhang H, Sissons S, Cox K, McNulty AM, Parsons SH, Wang T, Sams L, Geeganage S, Douglass LE, Neubauer BL, Dean NM, Blanchard K, Shou J, Stancato LF, Carter JH, Marcusson EG,
JournalJ Clin Invest
PubMed ID17786246
Expression of eukaryotic translation initiation factor 4E (eIF4E) is commonly elevated in human and experimental cancers, promoting angiogenesis and tumor growth. Elevated eIF4E levels selectively increase translation of growth factors important in malignancy (e.g., VEGF, cyclin D1) and is thereby an attractive anticancer therapeutic target. Yet to date, no eIF4E-specific ... More
Coordination between the actin cytoskeleton and membrane deformation by a novel membrane tubulation domain of PCH proteins is involved in endocytosis.
AuthorsTsujita K, Suetsugu S, Sasaki N, Furutani M, Oikawa T, Takenawa T,
JournalJ Cell Biol
PubMed ID16418535
The conserved FER-CIP4 homology (FCH) domain is found in the pombe Cdc15 homology (PCH) protein family members, including formin-binding protein 17 (FBP17). However, the amino acid sequence homology extends beyond the FCH domain. We have termed this region the extended FC (EFC) domain. We found that FBP17 coordinated membrane deformation ... More
Disruption of the checkpoint kinase 1/cell division cycle 25A pathway abrogates ionizing radiation-induced S and G2 checkpoints.
Checkpoint kinase (Chk)1 is an evolutionarily conserved protein kinase that was first identified in fission yeast as an essential component of the DNA damage checkpoint. In mice, Chk1 provides an essential function in the absence of environmentally imposed genotoxic stress. Here we show that human cells lacking Chk1 exhibit defects ... More
Ubiquitination-dependent cofactor exchange on LIM homeodomain transcription factors.
The interactions of distinct cofactor complexes with transcription factors are decisive determinants for the regulation of gene expression. Depending on the bound cofactor, transcription factors can have either repressing or transactivating activities. To allow a switch between these different states, regulated cofactor exchange has been proposed; however, little is known ... More
Purification and molecular characterization of cGMP-dependent protein kinase from Apicomplexan parasites. A novel chemotherapeutic target.
Authors Gurnett Anne M; Liberator Paul A; Dulski Paula M; Salowe Scott P; Donald Robert G K; Anderson Jennifer W; Wiltsie Judyann; Diaz Carmen A; Harris Georgiana; Chang Ben; Darkin-Rattray Sandra J; Nare Bakela; Crumley Tami; Blum Penny Sue; Misura Andrew S; Tamas Tamas; Sardana Mohinder K; Yuan Jeffrey; Biftu Tesfaye; Schmatz Dennis M;
JournalJ Biol Chem
PubMed ID11834729
The trisubstituted pyrrole 4-[2-(4-fluorophenyl)-5-(1-methylpiperidine-4-yl)-1H-pyrrol-3-yl]pyridine (Compound 1) inhibits the growth of Eimeria spp. both in vitro and in vivo. The molecular target of Compound 1 was identified as cGMP-dependent protein kinase (PKG) using a tritiated analogue to purify a approximately 120-kDa protein from lysates of Eimeria tenella. This represents the first ... More
Growth inhibitory factor prevents neurite extension and the death of cortical neurons caused by high oxygen exposure through hydroxyl radical scavenging.
Growth inhibitory factor (GIF), a brain-specific member of the metallothionein family (MT-III), has been characterized as a inhibitory substance for neurotrophic factors in Alzheimer's disease brains. However, the function of GIF, other than the inhibition of neurotrophic factors, remains unknown. We demonstrate here that exogenous GIF prevents neurite extension of ... More
Presenilin and nicastrin regulate each other and determine amyloid beta-peptide production via complex formation.
Amyloid beta-peptide (Abeta) is generated by the consecutive cuts of two membrane-bound proteases. Beta-secretase cuts at the N terminus of the Abeta domain, whereas gamma-secretase mediates the C-terminal cut. Recent evidence suggests that the presenilin (PS) proteins, PS1 and PS2, may be gamma-secretases. Because PSs principally exist as high molecular ... More
AKT/PKB phosphorylation of p21Cip/WAF1 enhances protein stability of p21Cip/WAF1 and promotes cell survival.
Authors Li Ying; Dowbenko Donald; Lasky Laurence A;
JournalJ Biol Chem
PubMed ID11756412
p21(Cip1/WAF1) (p21), a p53-inducible protein, is a critical regulator of cell cycle and cell survival. p21 binds to and inhibits both the DNA synthesis regulator proliferating cell nuclear antigen and cyclin A/E-CDK2 complexes. Recently, p21 has also been shown to be a positive regulator of cell cycle progression as p21 ... More
Anti-apoptotic Signaling of Pleiotrophin through Its Receptor, Anaplastic Lymphoma Kinase.
Authors Bowden Emma T; Stoica Gerald E; Wellstein Anton;
JournalJ Biol Chem
PubMed ID12107166
The secreted growth factor pleiotrophin (PTN) can induce mitogenesis in cells that express the receptor for this growth factor, anaplastic lymphoma kinase (ALK). Here we examine the ability of PTN to produce anti-apoptotic signals. We demonstrate that PTN is a survival factor for SW-13 epithelial cells and show that ribozyme-mediated ... More
The hypocholesterolemic agent LY295427 up-regulates INSIG-1, identifying the INSIG-1 protein as a mediator of cholesterol homeostasis through SREBP.
Authors Janowski Bethany A;
JournalProc Natl Acad Sci U S A
PubMed ID12242342
Oxysterols regulate cholesterol homeostasis through liver X receptor (LXR; cholesterol-lowering)- and sterol regulatory element-binding protein (SREBP; cholesterol-raising)-mediated signaling pathways. Previously we reported that the hypocholesterolemic agent LY295427 (4alpha-allylcholestan-3alpha-ol) reverses oxysterol-mediated suppression of SREBP processing. We now report that LY295427 increases expression of insulin-induced gene-1 (INSIG-1) and restores SREBP processing in ... More
Replicating hepatitis delta virus RNA is edited in the nucleus by the small form of ADAR1.
Authors Wong Swee Kee; Lazinski David W;
JournalProc Natl Acad Sci U S A
PubMed ID12399548
Hepatitis delta virus (HDV) uses a host-encoded RNA-editing activity to express its two essential proteins from the same coding sequence. Adenosine deaminase that acts on RNA (ADAR)1 and ADAR2 are enzymes that catalyze such reactions, and each, when overexpressed, are capable of editing HDV RNA in vivo. However, the enzyme ... More
Biological models and genes of tumor reversion: Cellular reprogramming through tpt1/TCTP and SIAH-1.
Tumor reversion is the process by which some cancer cells lose their malignant phenotype. This study was aimed at defining some of the molecular and phenotypic properties of this process. Biological models of tumor reversion were isolated from human leukemia and breast cancer cell lines by using the H-1 parvovirus ... More