ETS-RELATED PROTEIN ELK-1 IS HOMOLOGOUS TO THE C-FOS REGULATORY FACTOR P62TCF

A KEY event in the response of cells to proliferative signals is the rapid, transient induction of the c-fos proto-oncogene, which is mediated through the serum response element (SRE) in the fos promoter 1-4. Genomic footprinting 5,6 and transfection experiments 7-9 suggest that this activation occurs through a ternary complex that includes the serum response factor (SRF) 10 and the ternary complex factor p62 (ref. 7). Interaction of p62TCF with the SRF-SRE binary complex requires a CAGGA tract immediately upstream of the SRE (ref. 7). Proteins of the ets proto-oncogene family bind to similar sequences 11-13 and we have found that a member of this family, Elk-1 (ref. 14), forms SRF-dependent ternary complexes with the SRE. Elk-1 and p62TCF have the same DNA sequence requirements and antibodies against Elk-1 block the binding of both proteins. Furthermore, we show that like P62TCF, Elk-1 forms complexes with the yeast SRF-homologue MCM1 but not with yeast ARG80 (ref. 15). But ARG80 mutants that convey interaction with p62TCF can also form complexes with Elk-1. The similarity, or even identity, between Elk-1 and p62TCF suggests a novel regulatory role for Ets proteins that is effected through interaction with other proteins, such as SRF. Furthermore, the possible involvement of an Ets protein in the control of c-fos has interesting implications for proto-oncogene cooperation in cellular growth control 16.