Regulatory function of the P295-T311 motif of the estrogen receptor a - does proteasomal degradation induce emergence of peptides implicated in estrogenic responses?

The way in which estrogen receptor alpha (ERalpha) mediates gene transcription and hormone-dependent cancer cell proliferation is now being largely reconsidered in view of several recent discoveries. ERalpha-mediated transcription appears to be a cyclic and transient process where the proteasome - and thus receptor degradation - plays a pivotal role. In view of our recent investigations, which demonstrate the estrogenic activity of a synthetic peptide corresponding to a regulatory motif of the receptor (ERalpha17p), we propose that ERalpha proteasomal degradation could induce the emergence of regulatory peptide(s). The latter would function as a signal and contribute to the ERalpha activation process, amplifying the initial hormonal stimulation and giving rise to sustained estrogenic response.