CAMP (C13orf8, ZNF828) is a novel regulator of kinetochore-microtubule attachment
CAMP (C13orf8, ZNF828) is a novel regulator of kinetochore-microtubule attachment
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DOI：
10.1038/emboj.2010.276
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发表时间：
2011-01-05
期刊：
影响因子：
11.4
通讯作者：
Tanaka, Kozo
中科院分区：
文献类型：
--
作者：
Itoh, Go;Kanno, Shin-ichiro;Tanaka, Kozo
微管与动粒的正确连接对于染色体的精确分离是必不可少的。本文报道了一种新的参与着丝粒-微管结合的蛋白质--染色体结合维持磷蛋白（CAMP）（C13 orf 8，ZNF 828）。CAMP是一种锌指蛋白，含有三个特征性的重复基序，称为WK，SPE和FPE基序。CAMP定位于染色体和纺锤体，包括动粒，并在有丝分裂期间在多个位点经历CDK 1依赖性磷酸化。CAMP耗尽的细胞表现出严重的染色体错位，这与K-纤维对建立姐妹动粒双取向后施加的张力的抵抗力差有关。我们发现，FPE区域，这是负责纺锤体和动粒定位，是必要的正确的染色体排列。含有锌指结构域的C-末端区域负调节染色体排列，并且FPE区域中的磷酸化抵消这种调节。CENP-E和CENP-F的动粒定位受到CAMP消耗的影响，并通过表达不能功能性地拯救CAMP消耗的CAMP突变体，将CENP-E和CENP-F作为CAMP的下游效应物。这些数据表明，CAMP是必需的，以维持运动编排微管附着在双向。The EMBO Journal（2011）30，130-144. doi：10.1038/doj.2010.276; 2010年11月9日在线发布
Proper attachment of microtubules to kinetochores is essential for accurate chromosome segregation. Here, we report a novel protein involved in kinetochore-tnicrotubule attachment, chromosome alignment-maintaining phosphoprotein (CAMP) (C13orf8, ZNF828). CAMP is a zinc-finger protein containing three characteristic repeat motifs termed the WK, SPE, and FPE motifs. CAMP localizes to chromosomes and the spindle including kinetochores, and undergoes CDK1-dependent phosphorylation at multiple sites during mitosis. CAMP-depleted cells showed severe chromosome misalignment, which was associated with the poor resistance of K-fibres to the tension exerted upon establishment of sister kinetochore bi-orientation. We found that the FPE region, which is responsible for spindle and kinetochore localization, is essential for proper chromosome alignment. The C-terminal region containing the zinc-finger domains negatively regulates chromosome alignment, and phosphorylation in the FPE region counteracts this regulation. Kinetochore localization of CENP-E and CENP-F was affected by CAMP depletion, and by expressing CAMP mutants that cannot functionally rescue CAMP depletion, placing CENP-E and CENP-F as downstream effectors of CAMP. These data suggest that CAMP is required for maintaining kinetochore-microtubule attachment during bi-orientation. The EMBO Journal (2011) 30, 130-144. doi:10.1038/emboj.2010.276; Published online 9 November 2010