DHHC-7 and -21 are palmitoylacyltransferases for sex steroid receptors.
DHHC-7 and -21 are palmitoylacyltransferases for sex steroid receptors.
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DOI：
10.1091/mbc.e11-07-0638
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发表时间：
2012-01
影响因子：
3.3
通讯作者：
Levin ER
中科院分区：
文献类型：
--
作者：
Pedram A;Razandi M;Deschenes RJ;Levin ER
Extranuclear sex steroid receptors require palmitoylation to traffic to the plasma membrane, where they activate signal transduction cascades. We identify DHHC-7 and -21 palmitoylacyltransferases as conserved enzymes for the three classes of sex steroid receptors. Classical estrogen, progesterone, and androgen receptors (ERs, PRs, and ARs) localize outside the nucleus at the plasma membrane of target cells. From the membrane, the receptors signal to activate kinase cascades that are essential for the modulation of transcription and nongenomic functions in many target cells. ER, PR, and AR trafficking to the membrane requires receptor palmitoylation by palmitoylacyltransferase (PAT) protein(s). However, the identity of the steroid receptor PAT(s) is unknown. We identified the DHHC-7 and -21 proteins as conserved PATs for the sex steroid receptors. From DHHC-7 and -21 knockdown studies, the PATs are required for endogenous ER, PR, and AR palmitoylation, membrane trafficking, and rapid signal transduction in cancer cells. Thus the DHHC-7 and -21 proteins are novel targets to selectively inhibit membrane sex steroid receptor localization and function.
