PDF(Pubmed)
Abstract：
ANP32e, a chaperone of H2A.Z, is receiving increasing attention because of its association with cancer growth and progression. An unanswered question is whether ANP32e regulates H2A.Z dynamics during the cell cycle; this could have clear implications for the proliferation of cancer cells. We confirmed that ANP32e regulates the growth of human U2OS cancer cells and preferentially interacts with H2A.Z during the G1 phase of the cell cycle. Unexpectedly, ANP32e does not mediate the removal of H2A.Z from chromatin, is not a stable component of the p400 remodeling complex and is not strongly associated with chromatin. Instead, most ANP32e is in the cytoplasm. Here, ANP32e preferentially interacts with H2A.Z in the G1 phase in response to an increase in H2A.Z protein abundance and regulates its protein stability. This G1-specific interaction was also observed in the nucleoplasm but was unrelated to any change in H2A.Z abundance. These results challenge the idea that ANP32e regulates the abundance of H2A.Z in chromatin as part of a chromatin remodeling complex. We propose that ANP32e is a molecular chaperone that maintains the soluble pool of H2A.Z by regulating its protein stability and acting as a buffer in response to cell cycle-dependent changes in H2A.Z abundance.
摘要：
ANP32e,H2A的监护人.Z,正受到越来越多的关注，因为它与癌症的生长和进展有关。一个未解决的问题是ANP32e是否调节H2A。细胞周期中的Z动力学；这可能对癌细胞的增殖有明确的影响。我们证实ANP32e调节人U2OS癌细胞的生长并优先与H2A相互作用。Z在细胞周期的G1期。出乎意料的是,ANP32e不介导H2A的去除。Z来自染色质，不是p400重塑复合物的稳定成分，并且与染色质没有强烈关联。相反，大多数ANP32e在细胞质中。这里,ANP32e优先与H2A相互作用。G1期的Z响应于H2A的增加。Z蛋白丰度和调节其蛋白稳定性。在核质中也观察到这种G1特异性相互作用，但与H2A的任何变化无关。Z丰度。这些结果挑战了ANP32e调节H2A丰度的观点。染色质中的Z作为染色质重塑复合物的一部分。我们建议ANP32e是维持H2A可溶性池的分子伴侣。Z通过调节其蛋白质稳定性并充当缓冲液以响应H2A的细胞周期依赖性变化。Z丰度。
