Sheldon L A, Kingston R E
Department of Molecular Biology, Massachusetts General Hospital, Boston 02114.
Genes Dev. 1993 Aug;7(8):1549-58. doi: 10.1101/gad.7.8.1549.
HSF2, one of the heat shock transcription factors in mammalian cells, is localized to the cytoplasm during normal growth and moves to the nucleus upon activation. Heat shock transcription factors in metazoans contain four hydrophobic heptad repeat sequences, three in the amino terminus and one in the carboxy terminus, which are predicted to form alpha-helical coiled-coil structures analogous to the leucine zipper. Here, we show that point mutations in either of two amino-terminal zippers or in the carboxy-terminal zipper disrupt normal localization of HSF2 and cause it to be constitutively nuclear. We demonstrate further that two sequences immediately surrounding the amino-terminal zipper domain are required for nuclear localization. These sequences fit the consensus for a bipartite nuclear localization signal (NLS). We suggest that interactions between the amino- and carboxy-terminal zippers normally mask the NLS sequences of HSF2 and that these interactions are disrupted upon activation to expose the NLS sequences and allow transport of HSF2 to the nucleus. We conclude that zipper domains can regulate subcellular localization.
热休克转录因子2（HSF2）是哺乳动物细胞中的热休克转录因子之一，在正常生长过程中定位于细胞质，激活后转移至细胞核。后生动物中的热休克转录因子包含四个疏水的七肽重复序列，三个在氨基末端，一个在羧基末端，预计会形成类似于亮氨酸拉链的α-螺旋卷曲螺旋结构。在这里，我们表明两个氨基末端拉链或羧基末端拉链中的任何一个发生点突变都会破坏HSF2的正常定位，并使其持续定位于细胞核。我们进一步证明，氨基末端拉链结构域周围的两个序列是核定位所必需的。这些序列符合双分型核定位信号（NLS）的共识。我们认为，氨基末端和羧基末端拉链之间的相互作用通常会掩盖HSF2的NLS序列，而这些相互作用在激活时会被破坏，从而暴露出NLS序列，并允许HSF2转运至细胞核。我们得出结论，拉链结构域可以调节亚细胞定位。
