Department of Microbiology and Immunology, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA 19107, USA.
Immunol Res. 2011 Dec;51(2-3):227-36. doi: 10.1007/s12026-011-8249-3.
RIP1 is an adaptor serine/threonine kinase associated with the signaling complex of death receptors (DRs) including Fas, TNFR1, and TRAIL-Rs which can initiate apoptosis. While DRs are dispensable throughout development, RIP1 deletion results in perinatal lethality. The developmental defect caused by absence of RIP1 remains unexplained. In previous studies, RIP1-deficient hematopoietic progenitors failed to reconstitute the T cell compartment and our recent data indicate a new role for RIP1 in TCR-induced activation of the pro-survival NF-κB pathway. Here, we show that RIP1 is also critical for B cell development. In addition, RIP1(-/-) B cells stimulated through LPS/TLR4 are impaired in NF-κB activation but have no major defect in the Akt pathway. Recently, RIP1 has also emerged as a critical player in necrosis-like death, necroptosis, in various cell lines. We have demonstrated that RIP1 deficiency can reverse the embryonic and T cell proliferation defects in mice lacking FADD, a caspase adaptor protein, which indicates a potential role for RIP1 in mediating in vivo necroptosis. We provide an overview and discussion of the accumulating data revealing insights into the diverse functions of RIP1 in survival and death signaling in lymphocytes.
RIP1 是一种衔接丝氨酸/苏氨酸激酶，与 Fas、TNFR1 和 TRAIL-Rs 等死亡受体（DR）的信号复合物相关，可引发细胞凋亡。虽然 DR 在整个发育过程中不是必需的，但 RIP1 的缺失会导致围产期致死。目前尚不清楚 RIP1 缺失引起的发育缺陷的原因。在之前的研究中，缺乏 RIP1 的造血祖细胞无法重建 T 细胞区室，而我们最近的数据表明 RIP1 在 TCR 诱导的抗细胞凋亡 NF-κB 通路激活中具有新的作用。在这里，我们表明 RIP1 对于 B 细胞的发育也是至关重要的。此外，通过 LPS/TLR4 刺激的 RIP1(-/-) B 细胞在 NF-κB 激活中受损，但在 Akt 通路中没有主要缺陷。最近，RIP1 也已成为各种细胞系中坏死样死亡（坏死性凋亡）的关键参与者。我们已经证明，RIP1 缺乏可以逆转缺乏 caspase 衔接蛋白 FADD 的小鼠的胚胎和 T 细胞增殖缺陷，这表明 RIP1 在介导体内坏死性凋亡中可能具有作用。我们提供了一个概述和讨论，介绍了越来越多的数据，这些数据揭示了 RIP1 在淋巴细胞中的存活和死亡信号转导中的多种功能。
