Intercellular trafficking of the nuclear oncoprotein DEK
Intercellular trafficking of the nuclear oncoprotein DEK
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DOI：
10.1073/pnas.1220751110
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发表时间：
2013-04-23
影响因子：
11.1
通讯作者：
Markovitz, David M.
中科院分区：
文献类型：
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作者：
Saha, Anjan K.;Kappes, Ferdinand;Markovitz, David M.
DEK 是一种生化上独特的保守非组蛋白，对整体异染色质完整性至关重要。此外，DEK 可以被分泌并充当趋化促炎因子。在这里，我们证明外源性 DEK 可以穿透细胞，转移到细胞核，并在那里执行其内源性核功能。引人注目的是，邻近细胞可以吸收滑膜巨噬细胞分泌的 DEK。 DEK 内化是硫酸乙酰肝素依赖性过程，DEK 敲低细胞摄取 DEK 可以纠正整体异染色质耗竭和 DNA 修复缺陷（这些细胞的表型畸变特征）。因此，这些发现统一了 DEK 的细胞外和细胞内活性，并表明这种涉及 DEK 的旁分泌环在染色质生物学中发挥作用。
DEK is a biochemically distinct, conserved nonhistone protein that is vital to global heterochromatin integrity. In addition, DEK can be secreted and function as a chemotactic, proinflammatory factor. Here we show that exogenous DEK can penetrate cells, translocate to the nucleus, and there carry out its endogenous nuclear functions. Strikingly, adjacent cells can take up DEK secreted from synovial macrophages. DEK internalization is a heparan sulfate-dependent process, and cellular uptake of DEK into DEK knockdown cells corrects global heterochromatin depletion and DNA repair deficits, the phenotypic aberrations characteristic of these cells. These findings thus unify the extracellular and intracellular activities of DEK, and suggest that this paracrine loop involving DEK plays a role in chromatin biology.