TRANSCRIPTIONAL COMPETENCE OF PML-RAR FUSION RECEPTOR

描述(改编自申请人的摘要)：急性早幼粒细胞白血病 白血病(APL)通常与染色体易位有关， 将未知功能的核蛋白与DNA和配体结合 视黄酸受体α结构域(RARα)。通过以下方式治疗 维甲酸诱导急性早幼粒细胞白血病临床缓解。该项目提出了一种 PML-RAR融合蛋白转录活性的检测 从痘苗病毒感染细胞中纯化的天然受体蛋白 向量。PML-RAR同源二聚体和异源二聚体的结合位点选择 与RXR的结合偏好将被确定并与原生的结合偏好进行比较 RXR-RAR杂二聚体。配体诱导的PML-RAR Will构象变化 并与RAR的类似变化进行比较。最后，一个In 体外转录实验将被用来检测 PML-RAR本身以及与RXR联合使用。

DESCRIPTION (Adapted from the applicant's abstract): Acute promyelocytic leukemia (APL) is generally associated with a chromosomal translocation that fuses a nuclear protein of unknown function with the DNA- and ligand-binding domains of retinoid acid receptor alpha (RAR alpha). Treatment with retinoid acid induces clinical remission in APL. This project proposes a test of the transcriptional competence of the PML-RAR fusion protein using native receptor proteins purified from cells infected with vaccinia virus vectors. Binding site preferences for the PML-RAR homodimer and heterodimer with RXR will be determined and compared to the binding preference of native RXR-RAR heterodimers. Ligand-induced conformational changes of PML-RAR will be determined and compared with similar changes in RAR. Finally, an in vitro transcription assay will be used to examine the functionality of PML-RAR by itself and in conjunction with RXR.