Meta-Biol

• Pathways

In addition to nuclear signaling, estrogen receptors also promote a rapid, transcription- and translation-independent signaling response from the plasma membrane (reviewed in Levin, 2005; Schwartz et al, 2016). In contrast to their classical nuclear counterparts, estrogen receptors that signal from the plasma membrane are lipid-modified by palmitoylation. The amino-acid sequence encompassing an exposed cysteine residue (Cys447 for ESR1 and Cys399 for ESR2) is conserved between other steroid hormone receptors (Marino and Ascenzi, 2006). Mutation of the target cysteine in this motif abrogates membrane localization and the rapid response to estrogen (Acconcia et al, 2004; Acconcia et al, 2005; Pedram et al, 2007; Pedram et al, 2011). Golgi-localized palmitoyltransferases ZDHHC7 and ZDHHC21 catalyze the transfer of palmitoyl to the cysteine residue in the estrogen receptor (Pedram et al, 2012).