Estrogen receptor-α (ERα) is a
steroid hormone-sensitive
transcription factor that plays a critical role in development of
breast cancer. The binding of
estrogen to ERα triggers the recruitment of transcriptional co-activators as well as chromatin remodeling factors to
estrogen-responsive elements (ERE) of ERα target genes. This process is tightly associated with post-translational modifications (PTMs) of ERα and its co-activators for promotion of transcriptional activation, which leads to proliferation of a large subset of
breast tumor cells. These PTMs include phosphorylation, acetylation, methylation, and conjugation by
ubiquitin and
ubiquitin-like proteins.
Ubiquitin-fold modifier 1 (UFM1), one of
ubiquitin-like proteins, has recently been shown to be ligated to activating signal co-integrator 1 (ASC1), which acts as a transcriptional co-activator of
nuclear receptors. Here, we discuss the mechanistic connection between ASC1 modification by UFM1 and ERα transactivation, and highlight how the interplay of these processes is involved in development of
breast cancer. We also discuss potential use of UFM1-conjugating system as therapeutic targets against not only
breast cancer but also other
nuclear receptor-mediated
cancers.