Barrier-to-autointegration factor phosphorylation on Ser-4 regulates emerin binding to lamin A in vitro and emerin localization in vivo
Barrier-to-autointegration factor phosphorylation on Ser-4 regulates emerin binding to lamin A in vitro and emerin localization in vivo
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DOI：
10.1091/mbc.e05-04-0356
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发表时间：
2006-03-01
影响因子：
3.3
通讯作者：
Wilson, KL
中科院分区：
文献类型：
--
作者：
Bengtsson, L;Wilson, KL
自整合屏障因子（BAF）是一种在增殖细胞中必不可少的保守的10 kDa染色质蛋白。BAF二聚体结合双链DNA、组蛋白H3、组蛋白H1.1、核纤层蛋白A和转录调节因子，加上emerin和其他LEM结构域核蛋白。二维凝胶分析表明，内源性的人类和非洲爪蟾BAF是posterallymodified的磷酸化和潜在的其他修改，他们是hyperphosphorylated有丝分裂过程中。BAF上不变的Ser-4残基是间期和有丝分裂期间磷酸化的主要位点。在HeLa细胞过表达的磷酸模拟BAF错义突变体S4 E，但不是S4 A，肠溶蛋白从核膜错误定位，这表明丝氨酸-4-nonphosphorylated BAF通常促进emerin本地化在核膜。支持这一模型，野生型BAF，而不是突变体S4 E增强emerin结合核纤层蛋白A在体外。因此，丝氨酸-4-未磷酸化的BAF在定位Emerin中具有积极作用;这种作用可能与疾病相关，因为Emerin的丢失或错误定位导致Emery-Dreifuss肌营养不良症。我们的研究结果进一步表明，丝氨酸-4磷酸化抑制BAF结合emerin和核纤层蛋白A，从而削弱emerin-lamin相互作用在有丝分裂和间期。
Barrier-to-autointegration factor (BAF) is a conserved 10-kDa chromatin protein essential in proliferating cells. BAF dimers bind double-stranded DNA, histone H3, histone H1.1, lamin A, and transcription regulators, plus emerin and other LEM-domain nuclear proteins. Two-dimensional gel analysis showed that endogenous human and Xenopus BAF are posttranslationally modified by phosphorylation and potentially other modifications and that they are hyperphosphorylated during mitosis. The invariant Ser-4 residue on BAF is a major site of phosphorylation during both interphase and mitosis. In HeLa cells that overexpressed the phosphomimetic BAF missense mutant S4E, but not S4A, enterin mislocalized from the nuclear envelope, suggesting Ser-4-nonphosphorylated BAF normally promotes emerin localization at the nuclear envelope. Supporting this model, wild-type BAF but not mutant S4E enhanced emerin binding to lamin A in vitro. Thus, Ser-4-unphosphorylated BAF has a positive role in localizing emerin; this role may be disease relevant because loss or mislocalization of emerin causes Emery-Dreifuss muscular dystrophy. Our findings further suggest Ser-4 phosphorylation inhibits BAF binding to emerin and lamin A, and thereby weakens emerin-lamin interactions during both mitosis and interphase.