Jacob Justin T, Nair Raji R, Poll Brian G, Pineda Christopher M, Hobbs Ryan P, Matunis Michael J, Coulombe Pierre A
Department of Biochemistry and Molecular Biology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD 21205, USA.
Department of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
J Cell Sci. 2020 Oct 30;133(20):jcs254094. doi: 10.1242/jcs.254094.
Keratin 17 (; 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 -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 ) 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.This article has an associated First Person interview with the first author of the paper.
角蛋白17（K17）是一种非核纤层中间丝蛋白，最近发现它存在于细胞核中。我们在此报告K17依赖性的核形态、染色质组织和细胞增殖差异。缺乏K17的人类肿瘤角质形成细胞系的细胞核相对于正常细胞核更扁平。野生型K17的重新表达可挽救缺失K17细胞的核形态，但缺乏完整核定位信号（NLS）的突变形式则不能。对来自表达带有突变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了与K17相互作用的核蛋白，这些核蛋白在基因表达、染色质组织和RNA加工中具有已知作用。在缺乏K17的情况下，关键组蛋白修饰和LAP2β（由其编码的一种同工型）在细胞核内的定位会发生改变，这与细胞增殖减少和GLI1靶基因的抑制相关。因此，核K17影响核形态，并对上皮细胞中的染色质组织、基因表达和增殖产生相关影响。本文有对该论文第一作者的相关第一人称访谈。
