由核 CK2α 复合物激活的细胞周期依赖性细胞增殖基因网络。
Cell cycle-dependent gene networks for cell proliferation activated by nuclear CK2α complexes.
发表日期:2024 Jan
作者:
Miwako Kato Homma, Ryuichiro Nakato, Atsushi Niida, Masashige Bando, Katsunori Fujiki, Naoko Yokota, So Yamamoto, Takeshi Shibata, Motoki Takagi, Junko Yamaki, Hiroko Kozuka-Hata, Masaaki Oyama, Katsuhiko Shirahige, Yoshimi Homma
来源:
Cellular & Molecular Immunology
摘要:
据报道,蛋白激酶 CK2α 的核表达在人类癌症中升高,但其在细胞中可变定位的机制尚不清楚。这项研究证明了核 CK2 和与细胞增殖相关的基因表达之间的功能联系。对静止的人类正常成纤维细胞的生长刺激和磷酸化蛋白质组学分析发现,CK2α 池在丝氨酸 7 处高度磷酸化。磷酸化的 CK2α 易位到细胞核中,这种磷酸化似乎对于核定位和催化活性至关重要。与核 CK2 复合物相关的蛋白质特征揭示了细胞周期 G1 期过程中明显独特的转录因子和染色质重塑因子的富集。染色质免疫沉淀测序分析表明,CK2α 被招募到活性基因位点,G1 期晚期比 G1 早期更丰富,特别是在核心组蛋白基因、生长刺激相关基因和核糖体 RNA 的转录起始位点。我们的研究结果表明,核 CK2α 复合物通过激活组蛋白基因并触发核糖体生物发生,可能对促进细胞周期的进展至关重要,这与核和核仁转录调节因子有关。© 2023 Homma et al.
Nuclear expression of protein kinase CK2α is reportedly elevated in human carcinomas, but mechanisms underlying its variable localization in cells are poorly understood. This study demonstrates a functional connection between nuclear CK2 and gene expression in relation to cell proliferation. Growth stimulation of quiescent human normal fibroblasts and phospho-proteomic analysis identified a pool of CK2α that is highly phosphorylated at serine 7. Phosphorylated CK2α translocates into the nucleus, and this phosphorylation appears essential for nuclear localization and catalytic activity. Protein signatures associated with nuclear CK2 complexes reveal enrichment of apparently unique transcription factors and chromatin remodelers during progression through the G1 phase of the cell cycle. Chromatin immunoprecipitation-sequencing profiling demonstrated recruitment of CK2α to active gene loci, more abundantly in late G1 phase than in early G1, notably at transcriptional start sites of core histone genes, growth stimulus-associated genes, and ribosomal RNAs. Our findings reveal that nuclear CK2α complexes may be essential to facilitate progression of the cell cycle, by activating histone genes and triggering ribosomal biogenesis, specified in association with nuclear and nucleolar transcriptional regulators.© 2023 Homma et al.