A C-Terminal Acidic Domain Regulates Degradation of the Transcriptional Coactivator Bob1

John M. Lindner; Christina S. F. Wong; Andreas M?ller; Peter J. Nielsen

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A C-Terminal Acidic Domain Regulates Degradation of the Transcriptional Coactivator Bob1

机译：C末端酸性域调节转录共激活因子Bob1的降解。

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Bob1 (Obf-1 or OCA-B) is a 34-kDa transcriptional coactivator encoded by the Pou2af1 gene that is essential for normal B-cell development and immune responses in mice. During lymphocyte activation, Bob1 protein levels dramatically increase independently of mRNA levels, suggesting that the stability of Bob1 is regulated. We used a fluorescent protein-based reporter system to analyze protein stability in response to genetic and physiological perturbations and show that, while Bob1 degradation is proteasome mediated, it does not require ubiquitination of Bob1. Furthermore, degradation of Bob1 in B cells appears to be largely independent of the E3 ubiquitin ligase Siah. We propose a novel mechanism of Bob1 turnover in B cells, whereby an acidic region in the C terminus of Bob1 regulates the activity of degron signals elsewhere in the protein. Changes that make the C terminus more acidic, including tyrosine phosphorylation-mimetic mutations, stabilize the instable murine Bob1 protein, indicating that B cells may regulate Bob1 stability and activity via signaling pathways. Finally, we show that expressing a stable Bob1 mutant in B cells suppresses cell proliferation and induces changes in surface marker expression commonly seen during B-cell differentiation.

机译：Bob1（Obf-1或OCA-B）是由 Pou2af1 基因编码的34 kDa转录共激活因子，对小鼠正常B细胞发育和免疫应答至关重要。在淋巴细胞激活过程中，Bob1蛋白水平显着增加，而与mRNA水平无关，这表明Bob1的稳定性受到调节。我们使用基于荧光蛋白质的报告系统分析遗传和生理扰动的蛋白质稳定性，并显示，虽然Bob1降解是蛋白酶体介导的，但不需要Bob1的泛素化。此外，B细胞中Bob1的降解似乎很大程度上独立于E3泛素连接酶Siah。我们提出了一种在B细胞中Bob1周转的新机制，从而Bob1 C端的酸性区域调节了蛋白中其他地方的degron信号的活性。包括酪氨酸磷酸化模拟突变在内的使C末端更酸性的变化稳定了不稳定的鼠Bob1蛋白，表明B细胞可能通过信号传导途径调节Bob1的稳定性和活性。最后，我们表明在B细胞中表达稳定的Bob1突变体会抑制细胞增殖并诱导B细胞分化过程中常见的表面标志物表达变化。 展开▼

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《Molecular and Cellular Biology》 |2013年第23期|共13页

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John M. Lindner; Christina S. F. Wong; Andreas M?ller; Peter J. Nielsen;
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中图分类细胞生物学;

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2. Two functions of the C-terminal domain of Escherichia coli Rob: mediating "sequestration-dispersal" as a novel off-on switch for regulating Rob's activity as a transcription activator and preventing degradation of Rob by Lon protease. [J] . Fitzpatrick M Megan, Keen Edward F, Wolf Richard E Journal of Molecular Biology . 2009,第3期

机译：大肠杆菌Rob的C末端结构域的两个功能：介导“螯合分散”作为一种新型的关闭开关，用于调节Rob作为转录激活因子的活性并防止Lon蛋白酶降解Rob。

3. Two functions of the C-terminal domain of Escherichia coli Rob: mediating "sequestration-dispersal" as a novel off-on switch for regulating Rob's activity as a transcription activator and preventing degradation of Rob by Lon protease. [J] . Fitzpatrick M Megan, Keen Edward F, Wolf Richard E Journal of Molecular Biology . 2009,第3期

机译：大肠杆菌Rob的C末端结构域的两个功能：介导“螯合分散”作为一种新型的关闭开关，用于调节Rob作为转录激活因子的活性并防止Lon蛋白酶降解Rob。

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6. A C-Terminal Acidic Domain Regulates Degradation of the Transcriptional Coactivator Bob1 [O] . John M. Lindner, Christina S. F. Wong, Andreas Möller, 2013

机译：C末端酸性域调节转录共激活因子Bob1的降解。

7. The acidic C-terminal domain and A-box of HMGB-1 regulates p53-mediated transcription [O] . Banerjee, Sourav, Kundu, Tapas K. 2003

机译：HMGB-1的酸性C末端结构域和A-box调节p53介导的转录

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A C-Terminal Acidic Domain Regulates Degradation of the Transcriptional Coactivator Bob1

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