Different types of modification in c-fos and its associated protein p39: modulation of DNA binding by phosphorylation.

We have studied the biosynthesis and biochemical properties of the c-fos gene product and its associated protein (p39) in growth factor-stimulated fibroblasts. c-fos is a markedly acidic protein that is extensively post-translationally modified by phosphorylation and another type of modification not changing its relative molecular mass (Mr). More than 10 different forms of c-fos protein can be identified by two-dimensional gel analysis. In c-fos-transformed cells, however, most of the highly modified forms are missing. The affinity for DNA of less phosphorylated c-fos-protein complexes is higher than that of the highly modified ones. The transforming potential of c-fos protein and its affinity for DNA thus seems to be inversely correlated with the extent of its phosphorylation. In contrast to c-fos, p39 is a basic protein that is rendered even more basic by post-translational modification. Two other forms of p39 differing in specific domains of the protein (p41 and p43) were also found to be complexed with c-fos.