Nuclear import of sterol regulatory element-binding protein-2, a basic helix-loop-helix-leucine zipper (bHLH-Zip)-containing transcription factor, occurs through the direct interaction of importin beta with HLH-Zip.
Nuclear import of sterol regulatory element-binding protein-2, a basic helix-loop-helix-leucine zipper (bHLH-Zip)-containing transcription factor, occurs through the direct interaction of importin beta with HLH-Zip.
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DOI：
10.1091/mbc.10.7.2221
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发表时间：
1999-07
影响因子：
3.3
通讯作者：
E. Nagoshi;N. Imamoto;R. Sato;Y. Yoneda
中科院分区：
文献类型：
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作者：
E. Nagoshi;N. Imamoto;R. Sato;Y. Yoneda
甾醇调节元件结合蛋白 2 (SREBP-2) 是作为附着在内质网膜上的大前体分子产生的。为了响应甾醇的消耗，包含基本螺旋-环-螺旋-亮氨酸拉链结构域的前体的 N 端片段通过两次连续裂解释放并易位到细胞核，在那里激活靶基因的转录。本文的数据表明，释放的 SREBP-2 使用独特的核转运途径，该途径由导入蛋白 β 介导。当注射到细胞质中时，成熟形式的 SREBP-2 会主动转运到细胞核中。在缺少输入蛋白 α 的情况下，SREBP-2 直接与输入蛋白 β 结合。 Ran-GTP 而不是 Ran-GDP 会导致 SREBP-2-导入蛋白 β 复合物解离。 G19VRan-GTP 抑制活细胞中 SREBP-2 的核输入。在透化细胞体外转运系统中，SREBP-2 的核输入仅通过与 Ran 及其相互作用蛋白 p10/NTF2 结合的输入蛋白 β 来重建。我们进一步证明SREBP-2的螺旋-环-螺旋-亮氨酸拉链基序含有一种新型的核定位信号，它直接与输入蛋白β结合。
The sterol regulatory element-binding protein-2 (SREBP-2) is produced as a large precursor molecule attached to the endoplasmic reticulum membrane. In response to the sterol depletion, the N-terminal segment of the precursor, which contains a basic helix-loop-helix-leucine zipper domain, is released by two sequential cleavages and is translocated to the nucleus, where it activates the transcription of target genes. The data herein show that released SREBP-2 uses a distinct nuclear transport pathway, which is mediated by importin beta. The mature form of SREBP-2 is actively transported into the nucleus when injected into the cell cytoplasm. SREBP-2 binds directly to importin beta in the absence of importin alpha. Ran-GTP but not Ran-GDP causes the dissociation of the SREBP-2-importin beta complex. G19VRan-GTP inhibits the nuclear import of SREBP-2 in living cells. In the permeabilized cell in vitro transport system, nuclear import of SREBP-2 is reconstituted only by importin beta in conjunction with Ran and its interacting protein p10/NTF2. We further demonstrate that the helix-loop-helix-leucine zipper motif of SREBP-2 contains a novel type of nuclear localization signal, which binds directly to importin beta.