title: Methylation of high molecular weight fibroblast growth factor-2 determines post-translational increases in molecular weight and affects its intracellular distribution.
abstract: The high molecular weight (HMW) forms (24, 22.5, and 22 kDa) of basic fibroblast growth factor-2 (FGF-2) contain an N-terminal extension responsible for their predominantly nuclear localization. These forms of FGF-2 are post-translationally modified, resulting in a 1- to 2-kDa increase in apparent molecular mass. Here we show that this post-translational modification is inhibited by methionine starvation and by the methyltransferase inhibitors 5'-deoxy-5'-methylthioadenosine (MTA) and 3-deaza-adenosine. Inhibition of the methylation-dependent modification results in a significant decrease in HMW FGF-2 nuclear accumulation, suggesting that methylation is relevant to the intracellular distribution of these forms of FGF-2. Treatment with MTA does not affect either the synthesis or the intracellular fate of another nuclear protein, the SV40 large T antigen, demonstrating that this drug does not have a generalized effect on nuclear protein accumulation. These results link HMW FGF-2 post-translational modification to its intracellular distribution.
authors.affiliation: Department of Cell Biology, New York University Medical Center, New York 10016, USA.
authors.forename: G
authors.initials: G
authors.lastname: Pintucci
authors.forename: N
authors.initials: N
authors.lastname: Quarto
authors.forename: D B
authors.initials: DB
authors.lastname: Rifkin
mesh_terms: D016475:3T3 Cells; D000595:Amino Acid Sequence; D000818:Animals; D003839:Deoxyadenosines / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D016222:Fibroblast Growth Factor 2 / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D006168:Guinea Pigs; D006801:Humans; D066298:In Vitro Techniques; D008745:Methylation; D008780:Methyltransferases / Q000037:antagonists & inhibitors; D051379:Mice; D008969:Molecular Sequence Data; D008970:Molecular Weight; D011499:Protein Processing, Post-Translational; D013347:Subcellular Fractions / Q000378:metabolism; D013872:Thionucleosides / Q000494:pharmacology; D014162:Transfection; D014372:Tubercidin / Q000494:pharmacology
chemical_list: D003839:Deoxyadenosines; D004791:Enzyme Inhibitors; D013872:Thionucleosides; C018258:3-deazaadenosine; D016222:Fibroblast Growth Factor 2; C008500:5'-methylthioadenosine; D008780:Methyltransferases; D014372:Tubercidin