Fatty acid synthase mRNA binding protein

Abstract

Disclosed is a 178 kDa glucose-inducible human fatty acid synthase (FAS) mRNA binding protein which has been purified to homogeneity and its binding element characterized. This large phosphoprotein binds to a novel repetitive element in the 3′ untranslated region (UTR) of the FAS mRNA. In particular, the binding has been mapped to a 37 nucleotide stretch within the first 65 bases of the 3′ UTR of mRNA. The binding protein is useful for mediating FAS expression, for regulating lipoprotein secretion and cell growth and for screening of test compounds for activity as inhibitors of FAS.

What is claimed is:  
     
         1 . A glucose-inducible, phosphorylated mRNA binding protein having a molecular mass of 178+7 kDa and which binds to the 3′ untranslated region of the human fatty acid synthase mRNA.  
     
     
         2 . A binding protein of  claim 1  which binds to a 37 nucleotide stretch containing a repetitive ACCCC sequence within the first 65 bases of the 3′ untranslated region of the human fatty acid synthase mRNA.  
     
     
         3 . A binding protein of  claim 1  purified to homogeneity from human hepatoma cells.  
     
     
         4 . A binding element of the protein of  claim 1  comprising the 37 nucleotide sequence of SEQ ID NO: 4 .  
     
     
         5 . A 126 nucleotide transcript containing the proximal 3′ untranslated region of the human fatty acid synthase mRNA including the binding element of  claim 4  and having the nucleotide sequence of FIG. 8 (SEQ ID NO: 7 ).  
     
     
         6 . A method of mediating human fatty acid synthase gene expression comprising inhibiting or enhancing the binding activity of the binding protein of  claim 1  in human cells or in the metabolic pathway of a warm-blooded mammal.  
     
     
         7 . A method of regulating lipoprotein secretion and cell growth comprising inactivating or overexpressing the binding protein of  claim 1  in human cells.  
     
     
         8 . A method of screening test compounds for activity as inhibitors of human fatty acid synthase comprising determining the effect of a test compound on the binding activity of the binding protein of  claim 1.