Reactome | ZDHHC7, ZDHHC21 palmitoylate ESR1

ZDHHC7, ZDHHC21 palmitoylate ESR1

Stable Identifier

R-HSA-9021072

Type

Reaction [transition]

Species

Homo sapiens

Compartment

Golgi membrane

ReviewStatus

5/5

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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).

Literature References

PubMed ID	Title	Journal	Year
17424910	Steroid hormone rapid signaling: the pivotal role of S-palmitoylation Marino, M, Ascenzi, P	IUBMB Life	2006
15033483	S-palmitoylation modulates human estrogen receptor-alpha functions Acconcia, F, Ascenzi, P, Fabozzi, G, Visca, P, Marino, M	Biochem. Biophys. Res. Commun.	2004
17535799	A conserved mechanism for steroid receptor translocation to the plasma membrane Pedram, A, Razandi, M, Sainson, RC, Kim, JK, Hughes, CC, Levin, ER	J. Biol. Chem.	2007
22031296	DHHC-7 and -21 are palmitoylacyltransferases for sex steroid receptors Pedram, A, Razandi, M, Deschenes, RJ, Levin, ER	Mol. Biol. Cell	2012
25587652	Extranuclear steroid receptors are essential for steroid hormone actions Levin, ER	Annu. Rev. Med.	2015
15496458	Palmitoylation-dependent estrogen receptor alpha membrane localization: regulation by 17beta-estradiol Acconcia, F, Ascenzi, P, Bocedi, A, Spisni, E, Tomasi, V, Trentalance, A, Visca, P, Marino, M	Mol. Biol. Cell	2005
27288742	Rapid steroid hormone actions via membrane receptors Schwartz, N, Verma, A, Bivens, CB, Schwartz, Z, Boyan, BD	Biochim. Biophys. Acta	2016