Blokken Jolien, De Rijck Jan, Christ Frauke, Debyser Zeger
KU Leuven, Laboratory for Molecular Virology and Gene Therapy, Department of Pharmaceutical and Pharmacological Sciences, Leuven, Flanders, Belgium.
KU Leuven, Laboratory for Molecular Virology and Gene Therapy, Department of Pharmaceutical and Pharmacological Sciences, Leuven, Flanders, Belgium.
Drug Discov Today Technol. 2017 Jun;24:25-31. doi: 10.1016/j.ddtec.2017.11.002. Epub 2017 Nov 23.
Lens epithelium-derived growth factor p75 (LEDGF/p75), a transcriptional co-activator, plays an important role in tethering protein complexes to the chromatin. Through this tethering function LEDGF/p75 is implicated in a diverse set of human diseases including HIV infection and mixed lineage leukemia, an aggressive form of cancer with poor prognosis. Here we provide an overview of recent progress in resolving protein-protein and protein-chromatin interaction mechanisms of LEDGF/p75. This review will focus on two well-characterized domains, the PWWP domain and the integrase binding domain (IBD). The PWWP domain interacts with methylated lysine 36 in histone H3, a marker of actively transcribed genes. The IBD interacts with the IBD binding motif, available in cellular binding partners of LEDGF/p75. Each domain forms an interesting new target for drug discovery.
晶状体上皮衍生生长因子p75（LEDGF/p75）是一种转录共激活因子，在将蛋白质复合物栓系到染色质上发挥重要作用。通过这种栓系功能，LEDGF/p75与多种人类疾病有关，包括HIV感染和混合谱系白血病，后者是一种预后不良的侵袭性癌症。在此，我们概述了在解析LEDGF/p75的蛋白质-蛋白质和蛋白质-染色质相互作用机制方面的最新进展。本综述将聚焦于两个特征明确的结构域，即PWWP结构域和整合酶结合结构域（IBD）。PWWP结构域与组蛋白H3中甲基化的赖氨酸36相互作用，赖氨酸36是活跃转录基因的标志物。IBD与IBD结合基序相互作用，该基序存在于LEDGF/p75的细胞结合伙伴中。每个结构域都成为药物研发中一个有趣的新靶点。
