Motifs in the amino-terminus of CENP-A are required for its accumulation within the nucleus and at the centromere.

Motifs in the amino-terminus of CENP-A are required for its accumulation within the nucleus and at the centromere.
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CENP-A 氨基末端的基序是其在细胞核内和着丝粒处积累所必需的

DOI:
10.18632/oncotarget.17204
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发表时间:
2017-06-20
期刊:
影响因子:
--
通讯作者:
Zhu S
Zhu S
中科院分区:
其他
文献类型:
--
作者:
Jing R;Xi J;Leng Y;Chen W;Wang G;Jia W;Kang J;Zhu S

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着丝粒蛋白A(CENP-A)是核心组蛋白H3的变体,其标记着丝粒在染色体上的位置。将蛋白质靶向细胞核和着丝粒的机制尚未确定。在这项研究中,我们发现CENP-A的前53个而不是前29个氨基酸残基从氨基端缺失,导致其细胞质定位。两个基序,R42 R43 R44和K49 R52 K53 K56,据报道,这是所需的DNA接触在着丝粒核小体,被发现是至关重要的CENP-A核积累。这两个基序可能介导其与Importin-β的相互作用,但不参与CENP-A的着丝粒定位。第三个新的基序,L 60 L 61 I62 R63 K64,被发现是必不可少的CENP-A的着丝粒积累。非极性疏水残基L 60 L 61 I62,而不是碱性残基R63 K64,被认为是最重要的残基。蛋白质相互作用分析表明,该基序不参与CENP-A与其沉积因子的相互作用,但可能介导其与核心组蛋白H4和CENP-B的相互作用。我们的研究揭示了CENP-A的氨基末端在定位中的作用。
Centromere protein A (CENP-A) is a variant of core histone H3 that marks the centromere's location on the chromosome. The mechanisms that target the protein to the nucleus and the centromere have not been defined. In this study, we found that deletion of the first 53 but not the first 29 residues of CENP-A from the amino-terminus, resulted in its cytoplasmic localization. Two motifs, R42R43R44 and K49R52K53K56, which are reported to be required for DNA contact in the centromere nucleosome, were found to be critical for CENP-A nuclear accumulation. These two motifs potentially mediated its interaction with Importin-β but were not involved in CENP-A centromeric localization. A third novel motif, L60L61I62R63K64, was found to be essential for the centromeric accumulation of CENP-A. The nonpolar hydrophobic residues L60L61I62, but not the basic residues R63K64, were found to be the most important residues. A protein interaction assay suggested that this motif is not involved in the interaction of CENP-A with its deposition factors but potentially mediates its interaction with core histone H4 and CENP-B. Our study uncovered the role of the amino-terminus of CENP-A in localization.
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