ESR1 and cancer: The sex steroid 17 beta-estradiol (E2) reduces palmitoylation in a time- and dose-dependent manner.56 Palmitoylation cycling is more rapid for ESR1 than for ESR2, and depalmitoylation of these receptors mediates opposite functions on E2-exposed cancer cells: E2-induced depalmitoylation drives proliferation pathways (ERK/MAPK, PI3K/AKT, and PKC signaling associated with cell survival and cell cycle modulation, e.g., cyclin D1), whereas depalmitoylation of ESR2 drives proapoptotic activity (p38/MAPK signaling cascade involving caspase-3 activation and PARP cleavage).61