TRANSCRIPTIONAL COMPETENCE OF PML-RAR FUSION RECEPTOR

描述（改编自申请人摘要）：急性早幼粒细胞性 白血病（APL）通常与染色体易位有关， 融合了一种功能未知的核蛋白， 视黄酸受体α（RAR α）的结构域。 治疗 维甲酸诱导APL临床缓解。 该项目提出了一个 PML-RAR融合蛋白的转录能力的测试，使用 从被牛痘病毒感染的细胞中纯化的天然受体蛋白 向量。 PML-RAR同二聚体和异二聚体的结合位点偏好 与RXR的结合偏好将被确定并与天然的RXR的结合偏好进行比较。 RXR-RAR异二聚体。 配体诱导的PML-RAR构象变化将 确定并与RAR的类似变化进行比较。 最后，在 将使用体外转录测定来检查 PML-RAR本身以及与RXR结合使用。

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.