L-选择素在淋巴细胞归巢和白细胞滚动中起重要作用。越来越多的证据表明，它涉及许多疾病实体，包括糖尿病，缺血/再灌注损伤，炎症性疾病，和肿瘤转移。L-选择素在蛋白质水平的调节已经被充分表征。然而,人类L-选择素转录的调控在很大程度上仍然未知。为了解决L-选择素的转录调控，我们克隆了起始密码子ATG的1088bp5'。系列5'缺失突变体的荧光素酶分析位于-288/-1的核心启动子区域。通过5'RACE将主要转录起始位点定位在-115。转录因子Sp1、Ets1、Mzf1、Klf2和Irf1结合并转录激活L-选择蛋白启动子。重要的是,FOXO1与FOXO1基序结合，CCCTTTGG,在-87/-80，并以剂量依赖性方式反式激活L-选择蛋白启动子。组成型活性FOXO1的过表达增加了Jurkat细胞中内源性L-选择素的表达。我们得出结论，FOXO1通过靶向其启动子来调节L-选择素的表达。
L-selectin plays important roles in lymphocyte homing and leukocyte rolling. Mounting evidence shows that it is involved in many disease entities including diabetes, ischemia/reperfusion injuries, inflammatory diseases, and tumor metastasis. Regulation of L-selectin at protein level has been well characterized. However, the regulation of human L-selectin transcription remains largely unknown. To address transcriptional regulation of L-selectin, we cloned 1088 bp 5\' of the start codon ATG. Luciferase analysis of the serial 5\' deletion mutants located the core
promoter region at -288/-1. A major transcription initiation site was mapped at -115 by 5\'RACE. Transcription factors Sp1, Ets1, Mzf1, Klf2, and Irf1 bind to and transactivate the L-selectin
promoter. Significantly, FOXO1 binds to a FOXO1 motif, CCCTTTGG, at -87/-80, and transactivates the L-selectin
promoter in a dose-dependent manner. Over-expression of a constitutive-active FOXO1 increased the endogenous L-selectin expression in Jurkat cells. We conclude that FOXO1 regulates L-selectin expression through targeting its
promoter.
