The retinoblastoma tumour suppressor protein (RB) plays an important role in biological processes such as cell cycle control, DNA damage repair, epigenetic regulation, and genome stability. The canonical model of RB regulation is that cyclin-CDKs phosphorylate, and render RB inactive in late G1/S, promoting entry into S phase. Recently, mono-phosphorylated RB species were described to have distinct cell-cycle independent functions, suggesting that a phosphorylation code dictates diversity of RB function. However, a biologically relevant, functional role of RB phosphorylation at non-CDK sites has remained elusive. Here, we investigated S838/T841 dual phosphorylation, its upstream stimulus, and downstream functional output. We found that mimicking T-cell receptor activation in Jurkat leukemia cells induced sequential activation of downstream kinases including p38 MAPK, and RB S838/T841 phosphorylation. This signaling pathway disrupts RB and condensin II interaction with chromatin. Using cells expressing a WT or S838A/T841A mutant RB fragment, we present evidence that deficiency for this phosphorylation event prevents condensin II release from chromatin.

中文翻译：

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RB C 末端的磷酸化调节凝缩蛋白 II 从染色质中的释放

视网膜母细胞瘤肿瘤抑制蛋白（RB）在细胞周期控制、DNA损伤修复、表观遗传调控和基因组稳定性等生物过程中发挥着重要作用。RB调节的经典模型是细胞周期蛋白-CDK磷酸化，使RB在G1/S晚期失活，促进进入S期。最近，单磷酸化的 RB 物种被描述为具有独特的细胞周期独立功能，表明磷酸化密码决定了 RB 功能的多样性。然而，RB 在非 CDK 位点磷酸化的生物学相关功能作用仍然难以捉摸。在这里，我们研究了 S838/T841 双重磷酸化、其上游刺激和下游功能输出。我们发现模仿 Jurkat 白血病细胞中 T 细胞受体的激活会诱导下游激酶的连续激活，包括 p38 MAPK 和 RB S838/T841 磷酸化。该信号通路破坏 RB 和凝缩蛋白 II 与染色质的相互作用。使用表达 WT 或 S838A/T841A 突变 RB 片段的细胞，我们提供了证据表明，这种磷酸化事件的缺陷会阻止凝缩蛋白 II 从染色质中释放。