Cooperation of proto‐signals for nuclear accumulation of estrogen and progesterone receptors.
Cooperation of proto‐signals for nuclear accumulation of estrogen and progesterone receptors.
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雌激素和孕激素受体核积累的原始信号的合作。
DOI：
10.1002/j.1460-2075.1992.tb05453.x
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发表时间：
1992
期刊：
影响因子：
--
通讯作者：
P. Chambon
中科院分区：
文献类型：
--
作者：
T. Ylikomi;M. Bocquel;M. Berry;H. Gronemeyer;P. Chambon
用于核靶向的多种原信号（p-NLS），其中没有一种本身就足够了，在雌激素（ER）和孕激素（PR）受体中合作。在ER中，在激素结合结构域（HBD）中发现了雌激素诱导的p-NLS，此外还有三个富含赖氨酸/精氨酸的基序，类似于原型组成性核定位信号（NLS）。诱导型和组成型ER p-NLS在雌激素和羟基他莫昔芬存在下合作，但在ICI 164，384存在下不合作。在PR中，三个p-NLS，其中两个位于第二锌指内并直接邻近第二锌指，彼此合作，并在PR HBD中与弱激素诱导的p-NLS合作。对于ER和PR，没有观察到HBD对p-NLS的“掩蔽”，而无配体的糖皮质激素受体HBD抑制同源和异源NLS的活性。核共易位实验表明，在体内，ER和PR二聚体的稳定性是由同源配体控制的，但在不存在同源配体的情况下，ER二聚体比PR二聚体更稳定。这可能解释了ER和PR DNA体外结合的差异激素需求。
Multiple proto‐signals (p‐NLSs) for nuclear targeting, none of which suffices on its own, cooperate in the estrogen (ER) and progesterone (PR) receptors. In the ER, an estrogen‐inducible p‐NLS was found in the hormone binding domain (HBD), in addition to three lysine/arginine‐rich motifs resembling prototype constitutive nuclear localization signals (NLSs). The inducible and the constitutive ER p‐NLSs cooperate in the presence of estrogen and hydroxy‐tamoxifen, but not in the presence of ICI 164,384. In the PR, three p‐NLSs, two of which are located within and directly adjacent to the second zinc finger, cooperate with each other and a weak hormone‐inducible p‐NLS in the PR HBD. No ‘masking’ of p‐NLSs by the HBD was observed for ER and PR, while the ligand‐free glucocorticoid receptor HBD inhibited the activity of both homologous and heterologous NLSs. Nuclear co‐translocation experiments indicated that in vivo the stability of ER and PR dimers is hormonally controlled, but that, in the absence of the cognate ligand, ER dimers are more stable than PR dimers. This is likely to account for the differential hormone requirement of ER and PR DNA binding in vitro.