Abstract
17β-Estradiol (E2)-induced rapid functions (from seconds to minutes) can be attributed to a fraction of nuclear estrogen receptor-α (ERα) localized at the plasma membrane. As a potential mechanism, we postulated that S-palmitoylation of the Cys447 residue may explain the ability of ERα to associate to plasma membrane making possible E2-dependent rapid functions [e.g., extracellular regulated kinase (ERK) activation]. Here, we report direct evidence that the mutation of the Cys447 residue to Ala impairs human ERα palmitoylation and E2-induced rapid ERK phosphorylation when transfected in ER-devoid HeLa cells. Moreover, the Cys447Ala mutation significantly decreases the E2-induced transactivation of an estrogen responsive element construct probe. Similar effects were obtained treating HeLa cells transfected with wild type ERα with the palmitoyl-acyltransferase inhibitor 2-bromo- hexadecanoic acid. Moreover, the deletion of the A-D domains (containing the DNA binding region) of ERα had no consequences on [3H] palmitate incorporation, whereas no palmitoylation occurred in the ERα mutant devoid of the E domain (i.e., ligand binding domain). These results point to the pivotal role of the Cys447 residue in ERα palmitoylation and in the modulation of E2-induced non-genomic functions.
| Original language | English |
|---|---|
| Pages (from-to) | 878-883 |
| Number of pages | 6 |
| Journal | Biochemical and Biophysical Research Communications |
| Volume | 316 |
| Issue number | 3 |
| DOIs | |
| Publication status | Published - Apr 9 2004 |
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Keywords
- ERK
- Estrogen receptor-α
- Membrane estrogen receptor
- S-palmitoylation
- Transcriptional activity
ASJC Scopus subject areas
- Biochemistry
- Biophysics
- Molecular Biology
Cite this
S-palmitoylation modulates human estrogen receptor-α functions. / Acconcia, Filippo; Ascenzi, Paolo; Fabozzi, Giulia; Visca, Paolo; Marino, Maria.
In: Biochemical and Biophysical Research Communications, Vol. 316, No. 3, 09.04.2004, p. 878-883.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - S-palmitoylation modulates human estrogen receptor-α functions
AU - Acconcia, Filippo
AU - Ascenzi, Paolo
AU - Fabozzi, Giulia
AU - Visca, Paolo
AU - Marino, Maria
PY - 2004/4/9
Y1 - 2004/4/9
N2 - 17β-Estradiol (E2)-induced rapid functions (from seconds to minutes) can be attributed to a fraction of nuclear estrogen receptor-α (ERα) localized at the plasma membrane. As a potential mechanism, we postulated that S-palmitoylation of the Cys447 residue may explain the ability of ERα to associate to plasma membrane making possible E2-dependent rapid functions [e.g., extracellular regulated kinase (ERK) activation]. Here, we report direct evidence that the mutation of the Cys447 residue to Ala impairs human ERα palmitoylation and E2-induced rapid ERK phosphorylation when transfected in ER-devoid HeLa cells. Moreover, the Cys447Ala mutation significantly decreases the E2-induced transactivation of an estrogen responsive element construct probe. Similar effects were obtained treating HeLa cells transfected with wild type ERα with the palmitoyl-acyltransferase inhibitor 2-bromo- hexadecanoic acid. Moreover, the deletion of the A-D domains (containing the DNA binding region) of ERα had no consequences on [3H] palmitate incorporation, whereas no palmitoylation occurred in the ERα mutant devoid of the E domain (i.e., ligand binding domain). These results point to the pivotal role of the Cys447 residue in ERα palmitoylation and in the modulation of E2-induced non-genomic functions.
AB - 17β-Estradiol (E2)-induced rapid functions (from seconds to minutes) can be attributed to a fraction of nuclear estrogen receptor-α (ERα) localized at the plasma membrane. As a potential mechanism, we postulated that S-palmitoylation of the Cys447 residue may explain the ability of ERα to associate to plasma membrane making possible E2-dependent rapid functions [e.g., extracellular regulated kinase (ERK) activation]. Here, we report direct evidence that the mutation of the Cys447 residue to Ala impairs human ERα palmitoylation and E2-induced rapid ERK phosphorylation when transfected in ER-devoid HeLa cells. Moreover, the Cys447Ala mutation significantly decreases the E2-induced transactivation of an estrogen responsive element construct probe. Similar effects were obtained treating HeLa cells transfected with wild type ERα with the palmitoyl-acyltransferase inhibitor 2-bromo- hexadecanoic acid. Moreover, the deletion of the A-D domains (containing the DNA binding region) of ERα had no consequences on [3H] palmitate incorporation, whereas no palmitoylation occurred in the ERα mutant devoid of the E domain (i.e., ligand binding domain). These results point to the pivotal role of the Cys447 residue in ERα palmitoylation and in the modulation of E2-induced non-genomic functions.
KW - ERK
KW - Estrogen receptor-α
KW - Membrane estrogen receptor
KW - S-palmitoylation
KW - Transcriptional activity
UR - http://www.scopus.com/inward/record.url?scp=1642329884&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=1642329884&partnerID=8YFLogxK
U2 - 10.1016/j.bbrc.2004.02.129
DO - 10.1016/j.bbrc.2004.02.129
M3 - Article
C2 - 15033483
AN - SCOPUS:1642329884
VL - 316
SP - 878
EP - 883
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
SN - 0006-291X
IS - 3
ER -