PHRF1 促进了 CH12F3-2A 细胞中 IgA 的类别转换重组。
PHRF1 promotes the class switch recombination of IgA in CH12F3-2A cells.
机构信息
Institute of Biochemical Sciences, National Taiwan University, Taipei, Taiwan.
Graduate Institute of Immunology, National Taiwan University College of Medicine, Taipei, Taiwan.
出版信息
PLoS One. 2023 Aug 4;18(8):e0285159. doi: 10.1371/journal.pone.0285159. eCollection 2023.
PHRF1 is an E3 ligase that promotes TGF-β signaling by ubiquitinating a homeodomain repressor TG-interacting factor (TGIF). The suppression of PHRF1 activity by PML-RARα facilitates the progression of acute promyelocytic leukemia (APL). PHRF1 also contributes to non-homologous end-joining in response to DNA damage by linking H3K36me3 and NBS1 with DNA repair machinery. However, its role in class switch recombination (CSR) is not well understood. In this study, we report the importance of PHRF1 in IgA switching in CH12F3-2A cells and CD19-Cre mice. Our studies revealed that Crispr-Cas9 mediated PHRF1 knockout and shRNA-silenced CH12F3-2A cells reduced IgA production, as well as decreased the amounts of PARP1, NELF-A, and NELF-D. The introduction of PARP1 could partially restore IgA production in PHRF1 knockout cells. Intriguingly, IgA, as well as IgG1, IgG2a, and IgG3, switchings were not significantly decreased in PHRF1 deficient splenic B lymphocytes isolated from CD19-Cre mice. The levels of PARP1 and NELF-D were not decreased in PHRF1-depleted primary splenic B cells. Overall, our findings suggest that PHRF1 may modulate IgA switching in CH12F3-2A cells.
PHRF1 是一种 E3 连接酶，通过泛素化同源结构域抑制因子 TG 相互作用因子（TGIF）来促进 TGF-β 信号通路。PML-RARα 抑制 PHRF1 的活性，促进急性早幼粒细胞白血病（APL）的进展。PHRF1 还通过将 H3K36me3 和 NBS1 与 DNA 修复机制连接，在响应 DNA 损伤的非同源末端连接中发挥作用。然而，其在类别转换重组（CSR）中的作用尚不清楚。在这项研究中，我们报告了 PHRF1 在 CH12F3-2A 细胞和 CD19-Cre 小鼠中 IgA 转换中的重要性。我们的研究表明，CRISPR-Cas9 介导的 PHRF1 敲除和 shRNA 沉默的 CH12F3-2A 细胞减少了 IgA 的产生，同时降低了 PARP1、NELF-A 和 NELF-D 的含量。PARP1 的引入可以部分恢复 PHRF1 敲除细胞中的 IgA 产生。有趣的是，从 CD19-Cre 小鼠分离的脾 B 淋巴细胞中，PHRF1 缺陷并不显著降低 IgA 以及 IgG1、IgG2a 和 IgG3 的转换。PARP1 和 NELF-D 的水平在耗尽 PHRF1 的原代脾 B 细胞中没有降低。总的来说，我们的研究结果表明 PHRF1 可能调节 CH12F3-2A 细胞中的 IgA 转换。
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