ESTG binding induces ESR depalmitoylation

Stable Identifier
R-HSA-9027670
Type
Reaction [omitted]
Species
Homo sapiens
Compartment
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Palmitoylation of the estrogen receptor is dynamic. Binding of 17 beta-estradiol induces depalmitoylation by an unidentified protein palmitoyl hydrolase, releasing cytosolic ESRs that are free to interact with signaling proteins to initiate rapid non-genomic signaling (Marino et al, 2008; La Rosa et al, 2012; reviewed in Levin, 2005; Arnal et al, 2017). Dynamic palmitoylation cycles also impact the phosphorylation and degradation of ESR1. Mutation of C447 increases the susceptibility of ESR1 to degradation (La Rosa et al, 2012). Mutation of the palmitoyl acceptor cysteine 447 to alanine also abrogates phosphorylation of serine 118, a major N-terminal domain phosphorylation site that contributes to transcriptional activity. As phosphorylation of S118 itself likely occurs as a result of MAPK activation downstream of estrogen-stimulated membrane ESR1, the rapid non-genomic response to estrogen stimulation is interconnected with the classical transcriptional response.

Literature References
PubMed ID Title Journal Year
28539435 Membrane and Nuclear Estrogen Receptor Alpha Actions: From Tissue Specificity to Medical Implications

Arnal, JF, Lenfant, F, Métivier, R, Flouriot, G, Henrion, D, Adlanmerini, M, Fontaine, C, Gourdy, P, Chambon, P, Katzenellenbogen, B, Katzenellenbogen, J

Physiol. Rev. 2017
18206197 Membrane association of estrogen receptor alpha and beta influences 17beta-estradiol-mediated cancer cell proliferation

Marino, M, Ascenzi, P

Steroids 2008
22446104 Palmitoylation regulates 17β-estradiol-induced estrogen receptor-α degradation and transcriptional activity

La Rosa, P, Pesiri, V, Leclercq, G, Marino, M, Acconcia, F

Mol. Endocrinol. 2012
15705661 Integration of the extranuclear and nuclear actions of estrogen

Levin, ER

Mol. Endocrinol. 2005
Participants
Participant Of
Catalyst Activity
Catalyst Activity
Title
palmitoyl hydrolase activity of unknown palmitoyl-(protein) hydrolase [cytosol]
Physical Entity
Activity
Authored
Reviewed
Created