INCREASED ASSEMBLY OF CYTOSKELETAL PROTEINS ASSOCIATED WITH THE TRANSFORMATION OF HUMAN LIVER-CELLS INTO FIBROBLAST-LIKE CELLS

A topoisomerase II inhibitor. novobiocin, and a deacetylase inhibitor, butyrate, synergistically transformed human liver cells into fibroblast-like cells. This morphological change was associated with an increased production of procollagen type III peptide and a simultaneous assembly of actin, tubulin, vimentin and cytokeratin. Novobiocin and butyrate had no marked effect on the phosphorylation state of cytokeratin proteins, but synergistically enhanced [H-3]acetate uptake. From these results, it can be speculated that protein acetylation plays an important role in inducing the assembly of cytoskeletal proteins and the morphological transformation of human liver cells.