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PubMed2003

[Effect of the truncated human apoptosis-inducing factor expression on apoptosis of HeLa cells].

AIM: To observe the expression of the truncated human apoptosis-inducing factor (AIF) gene and its apoptosis-inducing effect on HeLa cells. METHODS: Full-length human AIF gene was cloned by RT-PCR, then the truncated AIF gene was constructed by deleting the N-terminal mitochondrial location sequence (MLS), and inserted into the EGFP co-expression vector pIRES2-EGFP. After being transfected into HeLa cells with Lipofectamin, the expression of the truncated AIF gene and its effect on HeLa cells morphology and growth condition were detected by fluorescence microscope, immunohistochemical staining, indirect fluoroimmunoassay and electron microscope analysis. RESULTS: The eukaryotic expression vector pIRES2-EGFP containing of truncated human AIF gene was constructed successfully. The AIF protein could be detected in the transfected HeLa cells. After transfection, typical apoptotic feature of the transfected HeLa cells and a mass of cell death were observed under electron microscope. CONCLUSION: The expression of the truncated human AIF gene can induce apoptosis of the transfected human HeLa cells.

Apoptosis↗
PubMed2005

[Detection of germline mutations in the APC gene with the protein truncation test].

The protein truncation test was established for analyzing mutations in the adenomatous polyposis coli (APC) gene which plays an important role in familial adenomatous polyposis (FAP). The sites of APC mutations and the clinic features of FAP patients were examined to find the relationship between them. Genomic DNA, which was extracted from peripheral blood lymphocytes of 22 FAP patients and the normal colon tissues of 43 sporadic colorectal cancers, were examined for mutations in exon15 of the APC gene by using PCR-TNT T7 Quick Coupled Tanscription/Translation System. The subsequent sequencing was used to confirm the mutation sites. Germline mutations were found in 5 of 22 FAP patients. All of the five mutations showed base pair deletions and led to produce truncated protein. No truncating germline mutation was found in normal tissues of 43 sporadic colorectal cancers. The protein truncation test is a sensitive and accurate technique to detect truncated mutations especially in the large exons of APC gene. It can be used as an routine method for assisting the early diagnosis of the FAP patients.

Adenomatous Polyposis Coli↗
PubMed1991

Evidence for endocytosis-dependent proteolysis in the generation of soluble truncated nerve growth factor receptors by A875 human melanoma cells.

We have identified nerve growth factor receptor (NGFR) on the cell surface and a truncated nerve growth factor receptor (NGFRt) in the conditioned medium of NGFR-negative cells that have been transfected with either the gene or the cDNA for the full-length receptor. By using cell surface iodination or metabolic labeling of A875 human melanoma cells, coupled with immunoprecipitation, we have determined the half-life of the cell-associated receptor to be approximately 7 h. Concomitant with receptor degradation is the accumulation of NGFRt in the extracellular medium. Approximately one-fifth of the labeled receptor can be recovered as the truncated species. These data support the hypothesis that NGFRt is generated by proteolysis of previously intact receptor. Furthermore, although no specific protease inhibitor assayed could affect this processing, NGFR degradation and truncation were retarded by treatment with: 1) the weak base amines, ammonium chloride or methylamine; 2) the carboxylic ionophore, monensin; or 3) the vacuolar ATPase inhibitor, bafilomycin A1, all agents that dissipate endosomal/lysosomal proton gradients via alternate mechanisms. Incubation of cells at 4 degrees C precluded NGFR degradation and truncation. The presence of ligand did not alter the time course of receptor truncation.

Ammonium Chloride↗
PubMed1991

Generation of the truncated form of the nerve growth factor receptor by rat Schwann cells. Evidence for post-translational processing.

These studies were initiated to determine whether the soluble, truncated form of the nerve growth factor (NGF) receptor arises from post-translational processing of the intact, membrane-bound receptor or from an alternatively spliced mRNA. Pulse-chase analysis of cultured primary rat Schwann cells coupled with immunoprecipitations using antibodies to the intracellular and extracellular domains of the receptor were used to monitor receptor production. Three forms of the NGF receptor (80, 83, and 85 kDa) displaying a precursor product relationship were detected over the 2-h chase period; only the 85-kDa species was detected on the cell surface. Truncated receptors (50 and 52 kDa) were detected in conditioned media 5 h after cell labeling but were never observed intracellularly. Polymerase chain reaction and RNase protection analyses of NGF receptor mRNA targeted toward the coding region for the transmembrane domain detected no splice variants that could generate truncated receptor, and media conditioned by fibroblasts transfected with rat receptor cDNA, in which splicing cannot occur, nonetheless contained the truncated receptor protein. Taken together, these results suggest that the truncated NGF receptor does not arise as a distinct translation product but rather from a post-translational modification of the intact, surface-bound form of the protein.

Amino Acid Sequence↗
PubMed1991

Expression of mouse mammary tumor virus glycoprotein truncations defines roles for the transmembrane domain and ectodomain hydrophobic region in constitutive exocytic trafficking and proteolytic processing.

A mutational analysis was used to identify structural domains that are important for exocytic transport and proteolytic cleavage of the mouse mammary tumor virus (MMTV) glycoprotein, which is expressed as a multidomain polyprotein. Rat HTC hepatoma cells were transfected with the MMTV glycoprotein gene driven by the constitutive Rous sarcoma virus promoter, with mutant genes encoding a series of polypeptide truncations or with a defective MMTV provirus containing a premature termination codon in the viral glycoprotein gene. Efficient proteolytic maturation and transport of MMTV glycoproteins to the cell surface or extracellular environment required the presence of the transmembrane domain but not the cytoplasmic tail. Two stable truncations retaining the hydrophobic region of the ectodomain in the absence of the transmembrane domain and cytoplasmic tail (trgp67 and trgp58) remained in endoglycosidase H sensitive and uncleaved forms. One of these truncations, trgp58, appeared to be tightly associated with intracellular membranes and strongly bound by heavy chain binding protein, whereas the other truncation, trgp67, was a soluble component of the lumen and persists intracellularly by a heavy chain binding protein-independent pathway. The truncated MMTV glycoprotein additionally lacking the hydrophobic region of the ectodomain was efficiently secreted. Taken together, our results demonstrate that the hydrophobic transmembrane domain of the MMTV glycoprotein is required for proper transport and proteolytic processing, whereas, in the absence of the transmembrane domain, the presence of a hydrophobic region of the ectodomain correlated with retention at an early step in the exocytic pathway.

Blotting, Northern↗
PubMed1991

Truncation of the extended carboxyl-terminal domain increases the expression and regulatory activity of the avian beta-adrenergic receptor.

A series of mutant avian beta-adrenergic receptors with progressively truncated carboxyl termini have been expressed in insect and mammalian cells. Removal of 18-124 amino acid residues caused multiple phenotypic changes in the receptor. Membranes from cells that expressed the truncated receptors displayed elevated basal (2- to 3-fold) and agonist-stimulated adenylylcyclase activities. Adenylylcyclase activity in these membranes also displayed greater stimulation in response to partial agonists. Activity was also markedly stimulated by beta-adrenergic ligands that are usually considered to be antagonists (alprenolol, greater than 4-fold; propranolol, approximately 2-fold). Wild type receptor did not mediate a response to these classical antagonists. After purification and reconstitution with Gs, the truncated receptors did not appear to be more active than the wild type. Guanine nucleotides modulated the affinity of agonist for the truncated receptors, whereas the affinity of agonist for the wild type receptor was not altered by guanine nucleotides. The truncated receptors were solubilized from the membrane more efficiently and were more susceptible to amino-terminal proteolysis than was the wild type protein. These results suggest interaction of the carboxyl terminus of the avian beta-adrenergic receptor with cellular regulatory or structural elements.

Adenylyl Cyclases↗
PubMed1991

Complete cDNA sequence of human complement pro-C5. Evidence of truncated transcripts derived from a single copy gene.

Two truncated human C5 clones, pHC5A and pHC5B, were isolated from an adult human liver cDNA library, and contained inserts of 2930 and 2181 bp, respectively. Both clones were polyadenylated and encoded the 5'-end of the C5 pro-molecule, thereby completing the human pro-C5 cDNA sequence. However, near the 3'-ends, at exon/intron boundaries, the nucleotide sequences of pHC5A and pHC5B diverged from each other and from the full-length 6.0-kb C5 cDNA sequence. Clone pHC5A, which overlapped the first human C5 clone described (J-16), encoded most of the C5 signal peptide, the complete beta-chain, the linker peptide, 177 amino acids of the alpha-chain, and contained 144 bp of Alu family consensus sequence encoding 48 amino acids of divergent protein sequence in an open reading frame. Clone pHC5B encoded the entire C5 signal peptide, the beta-chain, the linker peptide, nine amino acids of the alpha-chain, and six amino acids of divergent protein sequence in an open reading frame. Northern blot experiments demonstrated the presence of a 3.0-kb truncated C5 mRNA in adult human liver and a 4.8-kb truncated C5 mRNA in HepG2 cells in addition to the 6.0-kb full-length transcript. Truncated C5 mRNA were not detected in Raji, MOLT-4, human fibroblast or U937 cells, although the full-length 6.0-kb transcript was seen in MOLT-4 cells. Southern blot analyses indicated that the human C5 structural gene is large, complex, and is present in the human genome in a single copy, thereby demonstrating that the truncated C5 clones and mRNA are derived from a single C5 gene by alternative processing events.

Amino Acid Sequence↗
PubMed1988

Properties of a human insulin receptor with a COOH-terminal truncation. I. Insulin binding, autophosphorylation, and endocytosis.

In order to test the contribution of the insulin receptor COOH terminus to insulin action, a truncation of 43 COOH-terminal amino acids was engineered by cDNA-based deletion mutagenesis. This cDNA (HIR delta CT), as well as cDNA encoding the complete receptor (HIRc) was transfected into Rat 1 fibroblasts. Cells expressing 6.4 X 10(3) and 1.25 X 10(6) normal receptors and 2.5 X 10(5) HIR delta CT receptors, as well as control Rat 1 fibroblasts were selected for further analysis. All cell lines exhibited insulin binding of similar affinity. Partial tryptic digestion and immunoprecipitation by region-specific antibodies verified that the HIR delta CT receptors were truncated at the COOH terminus. Purified HIRc and HIR delta CT receptors underwent autophosphorylation with similar insulin and ATP sensitivity, although the HIR delta CT receptors were slightly more active in the absence of insulin. Transfected HIRc and HIR delta CT receptors undergo endocytosis in a normal fashion. Insulin internalization and degradation in both HIRc and HIR delta CT cells is increased in proportion to receptor number. Intracellular insulin processing, degradation, and release were qualitatively comparable among the transfected cell lines. Complete and truncated receptors internalize, recycle, and down-regulate normally. We conclude the following: 1) the COOH-terminal portion of the insulin receptor is not necessary for partial autophosphorylation or endocytosis; 2) following internalization the intracellular itinerary of the receptor and ligand appear normal with the truncated receptor; and 3) truncation of the COOH terminus does not impair recycling of the receptor or retroendocytosis of internalized ligand.

Animals↗
PubMed1988

The NH2-terminal 21 amino acid residues are not essential for the papain-inhibitory activity of oryzacystatin, a member of the cystatin superfamily. Expression of oryzacystatin cDNA and its truncated fragments in Escherichia coli.

Oryzacystatin, a proteinaceous cysteine proteinase inhibitor (cystatin) in rice, is comprised of 102 residues (Met1-Ala102) (Abe, K., Emori, Y., Kondo, H., Suzuki, K., and Arai, S. (1987) J. Biol. Chem. 262, 16793-16797). We constructed an expression plasmid containing a full length oryzacystatin cDNA at the multi-cloning site of pUC18 and produced a lacZ'-oryzacystatin fusion protein in Escherichia coli. The partially purified expressed protein efficiently inhibits papain activity assayed using N-benzoyl-DL-arginine-2-naphthylamide as a substrate. We also constructed expression plasmids lacking the 5'- and 3'-regions of cDNAs that encode NH2- and COOH-terminally truncated oryzacystatins. An N-truncated oryzacystatin lacking Gly5 and retaining Gln53-Val54-Val55-Ala56-Gly57 inhibited papain as efficiently as the full length oryzacystatin, although both Gly5 and Gln53-Gly57 (oryzacystatin numbering) are conserved among members of most cystatin superfamilies. However, another N-truncated oryzacystatin lacking the NH2-terminal 38 residues was almost completely inactive. On the other hand, a COOH-terminally truncated oryzacystatin lacking the COOH-terminal 11 residues possesses potent papain-inhibitory activity, whereas another COOH-terminally truncated oryzacystatin lacking 35 residues shows much less inhibitory activity, although it retains the two well conserved features Gly5 and Gln53-Gly57. These results indicate that the NH2-terminal 21 residues containing Gly5 and the COOH-terminal 11 residues are not essential, suggesting that a portion of the polypeptide segment containing Gln53-Gly57 is necessary for oryzacystatin to elicite its papain-inhibitory activity efficiently.

Amino Acid Sequence↗
PubMed1994

Bernard-Soulier syndrome Kagoshima: Ser 444-->stop mutation of glycoprotein (GP) Ib alpha resulting in circulating truncated GPIb alpha and surface expression of GPIb beta and GPIX.

The platelet membrane glycoprotein (GP)Ib/IX complex is composed of three polypeptides, GPIb alpha, GPIb beta, and GPIX, and functions as a platelet receptor for von Willebrand factor. All three subunits are reported to be requisite for efficient surface expression of the complex. The absence of the GPIb/IX complex on platelet membrane is the hallmark of a congenital qualitative platelet disorder, termed the Bernard-Soulier syndrome (BSS). We describe here the molecular basis of a novel variant phenotype of BSS in a female patient, designated as BSS Kagoshima. Her platelets completely lacked the surface expression of GPIb alpha, but expressed a residual amount of GPIb beta and GPIX. Unexpectedly, her platelets and plasma contained a truncated GPIb alpha polypeptide with an apparent molecular weight of 116 kD (under nonreducing conditions). The amounts of truncated protein were 23% and 60% of the normal values in platelets and plasma, respectively. The abnormal protein contained a normal amount of sialic acid as demonstrated by digestion with neuraminidase. DNA sequencing analysis showed a homozygous single nucleotide substitution from the serine codon (TCA) to a nonsense codon (TAA) at residue 444 in the GPIb alpha gene. The mutant gene generated a truncated GPIb alpha molecule lacking the transmembrane region and cytoplasmic tail. Her parents were heterozygotes for the mutation. These findings suggest that this type of truncated GPIb alpha was produced, normally glycosylated, and subsequently secreted into the plasma. Furthermore, the truncated GPIb alpha might be associated with the process of the surface expression of incomplete GPIb/IX complex, GPIb beta and GPIX.

Adult↗
PubMed1994

Biological activities of a putative truncated hepatitis B virus X gene product fused to a polylysin stretch.

Truncated transcripts terminating within the HBx frame have been recognized previously in tumor and liver tissue of HCC patients. In this study biological activities of a predicted truncated HBx fused to a polylysin stretch (HBtx-polylysin) and of full length HBx were compared in NIH3T3 cells transfected with respective cDNA plasmids. Transactivation of a co-transfecting reporter gene and influence on neor DNA mediated transformation to G418 resistance were determined. In comparison to full length HBx the data indicate for HBtx-polylysin a lower transactivating capacity and as judged by the yield of colonies on a solid surface, a lower capacity to stimulate neor DNA mediated transformation. In soft agar the outgrowth into G418 resistant colonies was dependent on co-transfecting HBx cDNA. In providing this condition HBtx-polylysin had a much higher relative activity than full length HBx. Large cointegrants consisting of the plasmids carrying truncated HBx cDNA and neor DNA respectively were identified by chromosomal in situ hybridization. Based on Southern blot analyses extended concatemeres of the HBx cDNA plasmid constituted a main part of the cointegrants. Expression of truncated HBx cDNA was followed on the RNA and the protein level. The presence of this cDNA could be correlated to a compact spindle like cell appearance, its loss after prolonged passaging in the absence of G418 to a concomitant reversion to the phenotype of the NIH3T3 cell. Interspersed selection for G418 resistance stabilized the morphologically transformed phenotype. These results provide a basis to manipulate expression of truncated HBx and to recognize thereby processes leading to transformation.

3T3 Cells↗
PubMed1993

Four new mutations in the apolipoprotein B gene causing hypobetalipoproteinemia, including two different frameshift mutations that yield truncated apolipoprotein B proteins of identical length.

Familial hypobetalipoproteinemia can be caused by mutations in the apolipoprotein (apo)B gene that interfere with the translation of a full-length apoB molecule. Frequently, a truncated apoB molecule can be detected in the plasma lipoproteins of affected subjects. In this report, we characterize four different apoB gene mutations causing hypobetalipoproteinemia that are associated with the synthesis of truncated apoB proteins. Two of the mutations are nonsense mutations caused by single nucleotide substitutions; these mutations are associated with the production of apoB-32.5 (1473 amino acids) and apoB-82 (3733 amino acids). The other two mutations are single nucleotide deletions (of apoB cDNA nucleotides 7295 and 7359, respectively). The altered reading frames created by these different frameshift mutations terminated with the same stop codon, and both therefore yielded a truncated protein of identical size: apoB-52.8 (2395 amino acids). The two apoB-52.8 proteins differ, however, in the number of novel carboxyl-terminal amino acids introduced by the frameshift. The buoyant density of lipoproteins containing the truncated apoBs was inversely related to the length of the truncated apoB. ApoB-32.5 was present only in high density lipoproteins (HDL) and the d > 1.21 g/ml fraction, whereas apoB-82 was present almost exclusively in very low density lipoproteins (VLDL). ApoB-52.8 was present primarily in VLDL, intermediate density lipoproteins (IDL), and low density lipoproteins (LDL); trace amounts were observed in the HDL.

Adult↗
PubMed1995

Heterologous expression of apolipoprotein B carboxyl-terminal truncates: a model for the study of lipoprotein biogenesis.

Expression of proteins in cells that lack specific chaperones, or subunits required for correct assembly results in the degradation of these proteins early on after synthesis, probably in the endoplasmic reticulum (ER) or an ER-related compartment. We have explored heterologous expression as a model to study the complex process involved in the biogenesis of apolipoprotein B (apoB)-containing lipoproteins. As an initial step, a series of carboxyl-terminal truncated apoB in COS cells were expressed to characterize this system. ApoB proteins ranging from apoB-13 to apoB-41 were expressed. Truncates larger than apoB-29 were completely retained and degraded within the cells; hence these cells have a 'secretory defect' for the larger truncates. Degradation of these apoB proteins is likely to be in the endoplasmic reticulum or ER-related compartment, as shown by sensitivity to endo beta-N-acetylglucosaminidase, by lack of an effect on the degradation kinetics by brefeldin A treatment, and by ImmunoGold EM. Degradation in COS cells was not affected by a variety of protease inhibitors, including N-acetyl-leucyl-leucyl-norleucinal (ALLN). Addition of oleate to the culture medium did not alter their metabolic fate. In comparison to the larger truncates, apoB proteins less than apoB-29 were partially secreted; the majority of these, too, were also retained and degraded intracellularly in a similar compartment. Secreted apoB-17 protein was shown to have been processed correctly in the Golgi and was secreted as a minimally lipidated protein. This model, based on the expression of apoB truncates larger than B-29 in COS cells, may therefore allow for the identification and study of the requirements of specific factors that may be required for both apoB secretion and lipoprotein biogenesis by in vivo complementation of this 'secretory' defect.

Amino Acid Sequence↗
PubMed1995

Differential expression of the full-length and secreted truncated forms of EGF receptor during formation of dental tissues.

The developmental regulation of various receptor forms may be a key-element in the local fine tuning of growth factor effects. The present study focuses on the tissue- and stage-specificity of the alternative splicing of EGF receptor transcripts in the rat incisor. In situ hybridization, as well as light- and electron-microscopic immunolocalization were performed with a set of tools which enable us to discriminate the full-length and secreted truncated forms of EGF receptor. Our data show that, apart from a transient expression in differentiating odontoblasts, EGF receptor expression was predominantly observed in the dental epithelium. In the crown, the expression of the full-length EGF receptor was maximal during preameloblast proliferation and differentiation, decreased in differentiated ameloblasts, and remained low throughout enamel secretion. On the other hand, maturation stage ameloblasts, which regulate the final mineralization of enamel, express high levels of the full-length EGF receptor. In contrast with ameloblasts, epithelial supra-ameloblastic cells, which are not directly involved in the deposition of enamel matrix, showed an alternating predominance of the secreted truncated form during the secretion stage, and the full-length form during the maturation stage. The presence of the secreted truncated EGF receptor form was supported by the electron microscopic detection of extracellular aggregates of immunoreactive EGF receptor. Finally, Northern-blotting of enamel organ samples confirmed the presence of transcripts corresponding to mRNAs of both EGF receptor forms. During root formation, a decreasing gradient of full-length EGF receptor form expression was observed from the apical loop to the disrupting zone in root epithelium. The secreted truncated EGF receptor form was essentially detected in epithelial cells of the disrupting zone of root epithelium. During crown formation, the secreted truncated EGF receptor form, which appears to be synthesized by epithelial supra-ameloblastic cells and secreted toward ameloblasts, may competitively bind EGF receptor ligands and modify activation of the full-length EGF receptor.

Aging↗
PubMed1996

Inhibition of p185neu kinase activity and cellular transformation by co-expression of a truncated neu protein.

The rat neu oncogene product encodes a 185 kDa receptor tyrosine kinase which is constitutively activated as a result of a single amino acid substitution (Val664-->Glu) within the transmembrane region. In this study, we show that the transforming activity of oncogenic p185neu (also termed Tneu) can be inhibited by co-expression of a truncated neu protein with a large cytoplasmic deletion (termed T691stop) which includes the tyrosine kinase domain. In cell lines co-expressing full-length and truncated neu proteins, we observed co-dimerization between full-length p185neu and truncated T691 stop, resulting in the formation of a kinase-inactive heteromeric complex. Phenotypic analysis of several different clones showed that the degree of inhibition of transformation in vitro and tumorigenicity in vivo was related to the ratio of full-length and truncated p185 proteins co-expressed in cells. These results provide evidence that expression of kinase-deficient neu proteins leads to co-dimerization that results in suppression of kinase activation and oncogenicity of associated p185neu-activated receptors. The mutant neu protein mediates inhibition in both transfected fibroblasts expressing oncogenic p185neu and mammalian cancer cells derived from a rat primary neuroglioblastoma expressing oncogenic p185neu. This truncated peptide may be important for the design of future therapies directed against erbB family oncoproteins.

Animals↗
PubMed1997

Potency of truncated secretory leukoprotease inhibitor assessed in acute lung injury models in hamsters.

We evaluated the potency of truncated secretory leukoprotease inhibitor (truncated SLPI) in a human sputum elastase (HSE)-induced lung injury model and in a specific neutrophil-mediated acute lung injury model in hamsters. Intratracheal administration of HSE induced acute lung hemorrhage that could be measured by determination of the hemoglobin content in the bronchoalveolar lavage fluid. Intratracheal administration of truncated SLPI 1 hr before HSE administration inhibited acute lung hemorrhage in a dose-dependent manner (ED50 = 46.8 microg/kg), as did i.v. injection of the inhibitor given 2 min before HSE administration (ED50 = 14.7 mg/kg). Intratracheal administration of endotoxin (lipopolysaccharide) induced pulmonary neutrophilia. Twenty-four hours after lipopolysaccharide administration, the addition of formyl-methionyl-leucyl-phenylalanine resulted in a neutrophil-dependent acute lung injury that expressed an increase in hemoglobin content and in elastase-like activity in bronchoalveolar lavage fluids. In this model, lung injury was significantly attenuated by i.v. and intratracheal administration of truncated SLPI. These results suggest that truncated SLPI appears to be a good candidate inhibitor for the treatment of destructive lung diseases due to neutrophils.

Animals↗
PubMed1998

Differential expression of a truncated form of the urokinase-type plasminogen-activator receptor in normal and tumor thyroid cells.

We studied the urokinase-type plasminogen activator (uPA) receptor (uPA-R) in normal and neoplastic human thyroid cells. It has recently been shown that cleaved forms of uPA-R display an extremely strong chemotactic activity. Normal human thyroid TAD-2 cells express the intact form of the uPA-R and a truncated form lacking the uPA-binding domain on their surface, in a similar manner to tumor thyroid cell lines. However, in tumor thyroid cell lines, the amount of the truncated form is variable: high in papillary carcinoma cells, very low in follicular carcinoma cells, and not detectable in anaplastic carcinoma cells. Similar studies on primary cell cultures confirm the presence of the truncated form of uPA-R in normal and in papillary carcinoma cells and its partial or total loss in follicular carcinoma cells. The presence of truncated uPA-R correlates to uPA secretion, except in papillary carcinoma cells, which express the truncated form of uPA-R but do not release uPA. uPA-R is also able to act as an adhesion receptor by binding vitronectin (VTN) and interacting with integrins. We observe that removal of uPA-R from the surface of normal thyroid and anaplastic carcinoma cells by phosphatidylinositol-specific phospholipase C or treatment with anti-uPA-R antibodies decreases the adhesion of both cell types to VTN and, less efficiently, to fibronectin or collagen. On the other hand, uPA treatment strongly increases the adhesion of anaplastic carcinoma cells specifically to VTN.

Cell Adhesion↗
PubMed1998

Synthetic full-length and truncated RANTES inhibit HIV-1 infection of primary macrophages.

OBJECTIVE: To determine the effect of beta-chemokines on HIV-1 infection of primary macrophages, and to search for chemokine derivatives devoid of biological effects but efficient at protecting CD4+ T lymphocytes and macrophages against HIV-1. DESIGN: Use of chemically synthesized molecules devoid of biological contaminants and monocyte-derived macrophages from healthy donors. METHODS: Full-length RANTES was chemically synthesized together with three derivatives, truncated of seven, eight and nine amino acids at the amino-terminus ([8-68]RANTES, [9-68]RANTES and [10-68]RANTES), which were tested for their biological activity and antiviral effects. RESULTS: Whereas full-length and truncated RANTES derivatives bound to beta-chemokine receptor CCR-5 with the same affinity as recombinant RANTES, the truncated forms were not chemotactic and acted as CCR-5 antagonists in this respect, although a partial agonist effect was noted on cell metabolism. Full-length RANTES and [8-68]RANTES protected T lymphocytes and macrophages from infection by HIV-1, although 10-fold higher concentrations of the truncated analogues were necessary to achieve the same effect as full-length RANTES. With regard to the effect of RANTES on HIV-1 infection of primary macrophages, our results contrast with most previously reported data. CONCLUSION: These data indicate that through binding to CCR-5, truncated RANTES derivatives that are devoid of detectable biological effects may represent candidates as drugs to protect both lymphocytes and macrophages from HIV- 1.

Animals↗