Liver-enriched Transcription Factor HNF-4 and Ubiquitous Factor NF-Y Are Critical for Expression of Blood Coagulation Factor X

SummaryIt is uncommon for similar pathways/systems to be involved in highly divergent functions within single organisms. Earlier, we have shown that trocarin D, a venom prothrombin activator, from the Australian rough-scaled snake Tropidechis carinatus, is structurally and functionally similar to the blood coagulation factor Xa (FXa). The presence of a haemostatic system in these snakes implies that they have two parallel prothrombin activating systems: one in the plasma, that participates in the life saving process of blood clotting and the other in their venom, where it acts as a toxin. Here, we report the complete cDNA sequence encoding the blood coagulation factor X (FX) from the liver of T. carinatus. Deduced T. carinatus FX sequence shows ~80% identity with trocarin D but ~50% identity with the mammalian FX. Our present study confirms the presence of two separate genes – one each for FX and trocarin D, that code for similar proteins in T. carinatus snake. These two genes have different expression sites and divergent uses suggesting that snake venom prothrombin activators have probably evolved by the duplication of the liver FX gene and subsequently marked for tissue-specific expression in the venom gland.

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Crystallization and preliminary X-ray study of blood coagulation factor IX/factor X-binding protein with anticoagulant activity from Habu snake venom

Journal of Molecular Biology ◽

10.1016/0022-2836(91)90008-t ◽

1991 ◽

Vol 220 (2) ◽

pp. 225-226 ◽

Cited By ~ 10

Author(s):

Hiroshi Mizuno ◽

Hideko Atoda ◽

Takashi Morita

Keyword(s):

Blood Coagulation ◽

Snake Venom ◽

Binding Protein ◽

Anticoagulant Activity ◽

Coagulation Factor ◽

Factor Ix ◽

Factor X ◽

X Ray ◽

Coagulation Factor Ix

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The contributions of Ca2+, phospholipids and tissue-factor apoprotein to the activation of human blood-coagulation factor X by activated factor VII

Biochemical Journal ◽

10.1042/bj2650327 ◽

1990 ◽

Vol 265 (2) ◽

pp. 327-336 ◽

Cited By ~ 141

Author(s):

V J J Bom ◽

R M Bertina

Keyword(s):

Tissue Factor ◽

Blood Coagulation ◽

Reaction Rate ◽

Factor Viia ◽

Coagulation Factor ◽

Fluid Phase ◽

Fold Increase ◽

Factor Vii ◽

Factor X ◽

Extrinsic Pathway

In the extrinsic pathway of blood coagulation, Factor X is activated by a complex of tissue factor, factor VII(a) and Ca2+ ions. Using purified human coagulation factors and a sensitive spectrophotometric assay for Factor Xa, we could demonstrate activation of Factor X by Factor VIIa in the absence of tissue-factor apoprotein, phospholipids and Ca2+. This finding allowed a kinetic analysis of the contribution of each of the cofactors. Ca2+ stimulated the reaction rate 10-fold at an optimum of 6 mM (Vmax. of 1.1 x 10(-3) min-1) mainly by decreasing the Km of Factor X (to 11.4 microM). In the presence of Ca2+, 25 microM-phospholipid caused a 150-fold decrease of the apparent Km and a 2-fold increase of the apparent Vmax. of the reaction; however, both kinetic parameters increased with increasing phospholipid concentration. Tissue-factor apoprotein contributed to the reaction rate mainly by an increase of the Vmax., in both the presence (40,500-fold) and absence (4900-fold) of phospholipid. The formation of a ternary complex of Factor VIIa with tissue-factor apoprotein and phospholipid was responsible for a 15 million-fold increase in the catalytic efficiency of Factor X activation. The presence of Ca2+ was absolutely required for the stimulatory effects of phospholipid and apoprotein. The data fit a general model in which the Ca2(+)-dependent conformation allows Factor VIIa to bind tissue-factor apoprotein and/or a negatively charged phospholipid surface resulting into a decreased intrinsic Km and an increased Vmax. for the activation of fluid-phase Factor X.

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Species D Adenoviruses as Oncolytic Viral Vectors

Viruses ◽

10.3390/v12121399 ◽

2020 ◽

Vol 12 (12) ◽

pp. 1399

Author(s):

Brianna L. Bullard ◽

Brigette N. Corder ◽

Eric A. Weaver

Keyword(s):

Blood Coagulation ◽

Cell Lines ◽

Cancer Cell ◽

Neutralizing Antibodies ◽

Coagulation Factor ◽

Cancer Cell Lines ◽

Factor X ◽

Multiple Cancer ◽

Iodide Uptake ◽

Oncolytic Adenoviruses

Oncolytic adenoviruses (Ad) have shown promising results in the therapeutic treatment of cancer. Ad type 5 (Ad5) is the most extensively utilized Ad type. However, several limitations exist to using Ad5 as an oncolytic virus, including high levels of anti-Ad5 neutralizing antibodies in the population, binding of the Ad5 hexon to blood coagulation factor X leading to liver sequestration and toxicity, and reduced expression of the primary receptor CAR on many tumors. Here, we use in vitro methods to explore the oncolytic potential of four alternative Ad types (Ad26, 28, 45, and 48) belonging to the species D Ad subgroup and developed replication-competent species D Ads expressing the human sodium iodide symporter protein (hNIS) for combination radiovirotherapy. We evaluated the species D Ad vectors transduction, replication, cytotoxicity, and gene expression in six different cancer cell lines. Species D Ads showed the greatest transduction and cytotoxic killing in the SKBR3 breast cancer cells, followed by 293, A549, and HepG2 cells, however the cytotoxicity was less than the wild type Ad5 virus. In contrast, species D Ads showed limited transduction and cytotoxicity in the Hela and SKOV3 cancer cell lines. These species D Ad vectors also successfully expressed the hNIS gene during infection leading to increased iodide uptake in multiple cancer cell lines. These results, the low seroprevalence of anti-species D antibodies, and the lack of binding to blood coagulation FX, support further exploration of species D Ads as alternative oncolytic adenoviruses against multiple types of cancer.

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A hexon-specific PEGylated adenovirus vector utilizing blood coagulation factor X

Biomaterials ◽

10.1016/j.biomaterials.2012.02.011 ◽

2012 ◽

Vol 33 (14) ◽

pp. 3743-3755 ◽

Cited By ~ 9

Author(s):

Hayato Matsui ◽

Fuminori Sakurai ◽

Kazufumi Katayama ◽

Tomoko Yamaguchi ◽

Sayuri Okamoto ◽

...

Keyword(s):

Blood Coagulation ◽

Coagulation Factor ◽

Adenovirus Vector ◽

Factor X

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The Interface between the EGF2 Domain and the Protease Domain in Blood Coagulation Factor IX Contributes to Factor VIII Binding and Factor X Activation

Biochemistry ◽

10.1021/bi060451h ◽

2006 ◽

Vol 45 (35) ◽

pp. 10777-10785 ◽

Cited By ~ 16

Author(s):

Caroline Fribourg ◽

Alexander B. Meijer ◽

Koen Mertens

Keyword(s):

Factor Viii ◽

Blood Coagulation ◽

Coagulation Factor ◽

Factor Ix ◽

Factor X ◽

Protease Domain ◽

Coagulation Factor Ix ◽

Factor X Activation

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Identification of a Binding Site For Blood Coagulation Factor Xa on the Heavy Chain of Factor Va. Amino Acid Residues 323−331 of Factor V Represent an Interactive Site for Activated Factor X†,‡

Biochemistry ◽

10.1021/bi026208+ ◽

2002 ◽

Vol 41 (42) ◽

pp. 12715-12728 ◽

Cited By ~ 13

Author(s):

Michael Kalafatis ◽

Daniel O. Beck

Keyword(s):

Amino Acid ◽

Binding Site ◽

Blood Coagulation ◽

Heavy Chain ◽

Factor Xa ◽

Coagulation Factor ◽

Factor V ◽

Amino Acid Residues ◽

Factor X ◽

Factor Va

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Inactivation of human blood coagulation factor X by chemical modification of gamma-carboxyglutamic acid residues

Biochemical and Biophysical Research Communications ◽

10.1016/0006-291x(84)90945-8 ◽

1984 ◽

Vol 124 (1) ◽

pp. 256-261 ◽

Cited By ~ 4

Author(s):

G.Bradley Sherrill ◽

David L. Straight ◽

Richard G. Hiskey ◽

Harold R. Roberts ◽

Michael J. Griffith

Keyword(s):

Chemical Modification ◽

Blood Coagulation ◽

Human Blood ◽

Coagulation Factor ◽

Factor X ◽

Carboxyglutamic Acid ◽

Human Blood Coagulation

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A candidate activation pathway for coagulation factor VII

Biochemical Journal ◽

10.1042/bcj20190595 ◽

2019 ◽

Vol 476 (19) ◽

pp. 2909-2926

Author(s):

Tina M. Misenheimer ◽

Kraig T. Kumfer ◽

Barbara E. Bates ◽

Emily R. Nettesheim ◽

Bradford S. Schwartz

Keyword(s):

Tissue Factor ◽

Blood Coagulation ◽

Factor Viia ◽

Coagulation Factor ◽

Factor Ix ◽

Factor Vii ◽

Factor X ◽

Contact Activation ◽

Coagulation Factor Vii ◽

Factor Viiia

Abstract The mechanism of generation of factor VIIa, considered the initiating protease in the tissue factor-initiated extrinsic limb of blood coagulation, is obscure. Decreased levels of plasma VIIa in individuals with congenital factor IX deficiency suggest that generation of VIIa is dependent on an activation product of factor IX. Factor VIIa activates IX to IXa by a two-step removal of the activation peptide with cleavages occurring after R191 and R226. Factor IXaα, however, is IX cleaved only after R226, and not after R191. We tested the hypothesis that IXaα activates VII with mutant IX that could be cleaved only at R226 and thus generate only IXaα upon activation. Factor IXaα demonstrated 1.6% the coagulant activity of IXa in a contact activation-based assay of the intrinsic activation limb and was less efficient than IXa at activating factor X in the presence of factor VIIIa. However, IXaα and IXa had indistinguishable amidolytic activity, and, strikingly, both catalyzed the cleavage required to convert VII to VIIa with indistinguishable kinetic parameters that were augmented by phospholipids, but not by factor VIIIa or tissue factor. We propose that IXa and IXaα participate in a pathway of reciprocal activation of VII and IX that does not require a protein cofactor. Since both VIIa and activated IX are equally plausible as the initiating protease for the extrinsic limb of blood coagulation, it might be appropriate to illustrate this key step of hemostasis as currently being unknown.

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