The relative cellular levels of CP2a and CP2b potentiates erythroid cell-specific expression of the α-globin gene by regulating the nuclear localization of CP2c
The relative cellular levels of CP2a and CP2b potentiates erythroid cell-specific expression of the α-globin gene by regulating the nuclear localization of CP2c
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DOI：
10.1016/j.bbrc.2009.01.172
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发表时间：
2009-03-20
影响因子：
3.1
通讯作者：
Kim, Chul Geun
中科院分区：
文献类型：
--
作者：
Chae, Ji Hyung;Kang, Ho Chul;Kim, Chul Geun
CP 2b通过与CP 2c和PIAS 1相互作用，以红系细胞特异性方式激活α-珠蛋白表达。尽管CP 2a与CP 2b相同，除了缺少编码另外36个氨基酸的外显子，并且具有固有的DNA结合和反式激活特性，但它在α-珠蛋白表达中不发挥任何作用。对外源CP 2蛋白的亚细胞定位研究表明，CP 2a和CP 2b分别只定位于细胞质和细胞核中。CP 2b特异性外显子负责CP 2b的核定位。有趣的是，CP 2c的亚细胞定位在细胞核或胞质溶胶中，这取决于CP 2a和CP 2b的相对水平，尽管CP 2c在不存在CP 2a/CP 2b的情况下固有地定位在胞质溶胶中。最后，在MEL细胞分化过程中，血红蛋白表达的显著增加与CP 2c的核转位相关。我们的数据表明，CP 2b增强红系细胞特异性α-珠蛋白的表达招募CP 2c到细胞核。(C)2009 Elsevier Inc. All rights reserved.
CP2b activates alpha-globin expression in an erythroid cell-specific manner, through interaction with CP2c and PIAS1. Although CP2a is identical to CP2b except for lacking an exon encoding additional 36 amino acids and has the intrinsic DNA binding and transactivation properties, it does not exert any role in alpha-globin expression. Investigation of subcellular localization of exogenous CP2 proteins revealed that CP2a and CP2b were exclusively localized in the cytosol and nucleus, respectively. The CP2b-specific exon was in charge of the nuclear localization of CP2b. Interestingly, subcellular localization of CP2c was either in the nucleus or cytosol depending on the relative level of CP2a and CP2b although CP2c intrinsically localized in the cytosol in the absence of CP2a/CP2b. Finally, dramatic increment of hemoglobin expression was correlated with nuclear translocation of CP2c during MEL cell differentiation. Our data suggest that CP2b potentiate erythroid cell-specific alpha-globin expression by recruiting CP2c into the nucleus. (C) 2009 Elsevier Inc. All rights reserved.