Keratin 17 (KRT17; K17), a non-lamin intermediate filament protein, was recently found to occur in the nucleus. We report here on K17-dependent differences in nuclear morphology, chromatin organization, and cell proliferation. Human tumor keratinocyte cell lines lacking K17 exhibit flatter nuclei relative to normal. Re-expression of wild-type K17, but not a mutant form lacking an intact nuclear localization signal (NLS), rescues nuclear morphology in KRT17-null cells. Analyses of primary cultures of skin keratinocytes from a mouse strain expressing K17 with a mutated NLS corroborated these findings. Proteomics screens identified K17-interacting nuclear proteins with known roles in gene expression, chromatin organization and RNA processing. Key histone modifications and LAP2β (an isoform encoded by TMPO) localization within the nucleus are altered in the absence of K17, correlating with decreased cell proliferation and suppression of GLI1 target genes. Nuclear K17 thus impacts nuclear morphology with an associated impact on chromatin organization, gene expression, and proliferation in epithelial cells.

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角蛋白 17（KRT17；K17）是一种非核纤层蛋白中间丝蛋白，最近被发现存在于细胞核中。我们在此报告核形态、染色质组织和细胞增殖方面 K17 依赖性差异。缺乏 K17 的人肿瘤角质形成细胞系表现出比正常细胞更扁平的细胞核。野生型 K17 的重新表达，而不是缺乏完整核定位信号 (NLS) 的突变形式，可以挽救KRT17缺失细胞中的核形态。对表达带有突变 NLS 的 K17 的小鼠品系的皮肤角质形成细胞原代培养物的分析证实了这些发现。蛋白质组学筛选鉴定出与 K17 相互作用的核蛋白，这些蛋白在基因表达、染色质组织和 RNA 加工中具有已知的作用。在缺乏 K17 的情况下，关键组蛋白修饰和 LAP2β（由TMPO编码的同种型）在细胞核内的定位发生改变，与细胞增殖减少和 GLI1 靶基因抑制相关。因此，核 K17 会影响核形态，并对上皮细胞的染色质组织、基因表达和增殖产生相关影响。

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