Dimer formation and conformational flexibility ensure cytoplasmic stability and nuclear accumulation of Elk-1

E. L. Evans , J. Saxton , S. J. Shelton , A. Begitt , N. D. Holliday , R. A. Hipskind (1) , P. E. Shaw

1 IGMM - Institut de Génétique Moléculaire de Montpellier

The ETS (E26) protein Elk-1 serves as a paradigm for mitogen-responsive transcription factors. It is multiply phosphorylated by mitogen-activated protein kinases (MAPKs), which it recruits into pre-initiation complexes on target gene promoters. However, events preparatory to Elk-1 phosphorylation are less well understood. Here, we identify two novel, functional elements in Elk-1 that determine its stability and nuclear accumulation. One element corresponds to a dimerization interface in the ETS domain and the second is a cryptic degron adjacent to the serum response factor (SRF)-interaction domain that marks dimerization-defective Elk-1 for rapid degradation by the ubiquitin-proteasome system. Dimerization appears to be crucial for Elk-1 stability only in the cytoplasm, as latent Elk-1 accumulates in the nucleus and interacts dynamically with DNA as a monomer. These findings define a novel role for the ETS domain of Elk-1 and demonstrate that nuclear accumulation of Elk-1 involves conformational flexibility prior to its phosphorylation by MAPKs.

Domaines: Génomique, Transcriptomique et Protéomique [q-bio.GN]

E. L. Evans, J. Saxton, S. J. Shelton, A. Begitt, N. D. Holliday, et al.. Dimer formation and conformational flexibility ensure cytoplasmic stability and nuclear accumulation of Elk-1. Nucleic Acids Research, 2011, 39 (15), pp.6390-402. ⟨10.1093/nar/gkr266⟩. ⟨hal-02193488⟩