Roles of phytanoyl-CoA alpha-hydroxylase in mediating the expression of human coagulation factor VIII.

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Chen C, Wang Q, Fang X, Xu Q, Chi C, Gu J

Roles of phytanoyl-CoA alpha-hydroxylase in mediating the expression of human coagulation factor VIII.

J Biol Chem. 2001 Dec 7;276(49):46340-6.

PubMed ID

11574539 [ View in PubMed

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Abstract

The coagulation factor VIII (FVIII) is the coagulation factor deficient in the X-chromosome-linked bleeding disorder hemophilia A. Previous transfection studies demonstrated that factor VIII was 10-100-fold less efficiently expressed than the homologous coagulation factor, factor V. To investigate the regulatory mechanisms of FVIII synthesis and secretion, we used the yeast two-hybrid system as an approach to search for proteins that associated with FVIII. The A2 domain (337-740 amino acids) of factor VIII (FVIII-A2) was used as a bait and phytanoyl-CoA alpha-hydroxylase (PAHX) was identified as a binding protein of FVIII-A2. PAHX had potential to interact with the residues 373-508 within the A2 domain, but not with A1 and A3 (the homologous domains of A2). The interaction between the A2 domain and PAHX was independent of the type 2 peroxisomal targeting signal (PTS2) of PAHX. Overexpression of PAHX in FVIII-produced cells decreased the expression of FVIII by about 70%. The elevated expression of von Willebrand factor had no effect on the suppression of FVIII secretion by PAHX. Expression of the green fluorescent PAHX fusion protein in SMMC-7721 cells affected the intracellular trafficking of FVIII-A2. These results suggested that the interaction between PAHX and FVIII-A2 was in part responsible for the low-level expression of factor VIII.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Antihemophilic factor, human recombinant	Phytanoyl-CoA dioxygenase, peroxisomal	Protein	Humans	Unknown	Antagonist	Details
Lonoctocog alfa	Phytanoyl-CoA dioxygenase, peroxisomal	Protein	Humans	Unknown	Antagonist	Details
Moroctocog alfa	Phytanoyl-CoA dioxygenase, peroxisomal	Protein	Humans	Unknown	Antagonist	Details