Center David M, Cruikshank William W, Zhang Yujun
The Pulmonary Center, Boston University School of Medicine, Boston, MA 02118, USA.
J Immunol. 2004 Feb 1;172(3):1654-60. doi: 10.4049/jimmunol.172.3.1654.
The precursor for IL-16 (pro-IL-16) is a nuclear and cytoplasmic PDZ domain-containing protein. In this study we have found that pro-IL-16 is absent or mutated in four T lymphoblastic leukemia cell lines examined. Ectopic expression of pro-IL-16 in pro-IL-16-negative Jurkat cells blocks cell cycle progression from G(0)/G(1) to S phase associated with elevated levels of the cyclin-dependent kinase inhibitor p27(KIP1). Pro-IL-16 decreases p27(KIP1) degradation by reducing transcription and subsequent expression of Skp2, a key component of the SCF(Skp2) ubiquitin E3 ligase complex. Taken together, these findings identify pro-IL-16 as a novel regulator of Skp2 expression and p27(KIP1) levels and implicate a role for pro-IL-16 in T cell proliferation.
白细胞介素-16（pro-IL-16）的前体是一种含有核和胞质PDZ结构域的蛋白质。在本研究中，我们发现在所检测的四种T淋巴母细胞白血病细胞系中，pro-IL-16缺失或发生了突变。在pro-IL-16阴性的Jurkat细胞中异位表达pro-IL-16可阻断细胞周期从G(0)/G(1)期向S期的进展，这与细胞周期蛋白依赖性激酶抑制剂p27(KIP1)水平升高有关。Pro-IL-16通过减少SCF(Skp2)泛素E3连接酶复合体的关键组分Skp2的转录及后续表达，降低p27(KIP1)的降解。综上所述，这些发现确定pro-IL-16是Skp2表达和p27(KIP1)水平的新型调节因子，并提示pro-IL-16在T细胞增殖中发挥作用。
