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The sequential phosphorylation of PHF10 subunit of the PBAF chromatin-remodeling complex determines different properties of the PHF10 isoforms

机译:PBAF染色质 - 重塑复合物的PHF10亚基的顺序磷酸化决定了PHF10同种型的不同性质

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The mammalian PBAF subfamily of SWI/SNF chromatin remodeling complexes plays a wide role in the regulation of gene expression. PHF10 is a subunit of the signature module of PBAF, responsible for its interaction with chromatin. PHF10 is represented by four different isoforms, which are alternatively incorporated in the complex. Two of PHF10 isoforms lacking C-terminal PHD domains contain a cluster of phosphorylated serine residues, designated as X-cluster. In the present study, we explore the phosphorylation of the X-cluster in detail. We identified additional phosphorylated serine residues and designated them as either frequently or rarely phosphorylated. The X-cluster consists of two independently phosphorylated subclusters. Phosphorylation of the second subcluster depends on phosphorylation of a primary serine 327. These two subdusters surround a sequence, which is predicted to be a nuclear localization sequence (NLS3). The NLS3 does not affect localization of PHF10 isoforms. However, it is essential for X-cluster phosphorylation and increased stability of isoforms that lack PHD. Conversely, the presence of NLS3 signal in isoforms that contain C-terminal PHD domains reduces their stability. Thus, phosphorylation of PHF10 isoforms regulates their cell level, determining the rate of incorporation in PBAF. This may alter the pattern of PBAF regulated genes.
机译:SWI / SNF染色质改造复合物的哺乳动物PBAF亚家族在基因表达的调节中起着广泛的作用。 PHF10是PBAF签名模块的亚基,负责其与染色质的相互作用。 PHF10由四种不同的同种型表示,其可选地结合在复合物中。缺乏C-末端PHD结构域的两种PHF10同种型含有磷酸化的丝氨酸残留物,指定为X簇。在本研究中,我们详细探讨了X簇的磷酸化。我们鉴定了额外的磷酸化丝氨酸残基,并以经常或很少磷酸化指定它们。 X簇由两个独立磷酸化的子平整板组成。第二亚聚蛋牙的磷酸化取决于初级丝氨酸327的磷酸化。这两个次级围绕序列,其预测是核定位序列(NLS3)。 NLS3不会影响PHF10同种型的定位。然而,对于缺乏磷博的同种型的X簇磷酸化和增加的稳定性至关重要。相反,含有C末端PHD结构域的同种型中的NLS3信号的存在降低了它们的稳定性。因此,PHF10同种型的磷酸化调节其细胞水平,确定PBAF中的掺入速率。这可能改变PBAF调节基因的模式。

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