SUPPRESSION OF V MYB TRANSFORMATION BY RAR AND RXR

描述 本提案的总体目标是了解 视黄酸受体-a抑制v-Myb的转化 癌蛋白 v-Myb转化单核细胞，巨噬细胞前体， 阻碍了他们的辨别能力。 然而， 外源性RAR-α进入v-Myb转化的BM 2细胞系允许巨噬细胞 分化响应维甲酸，尽管持续存在 v-Myb蛋白质。 因为RAR通常作为异二聚体起作用， RXR蛋白，RXR蛋白在该系统中的作用是研究的主要焦点。 下一个三年期。 理解的具体目标 RAR-a抑制v-Myb转化的机制是 以下内容： 1)RXR-a和RXR-a特异性单克隆抗体的制备; 2） RXR-α和表达RXR-α的BM 2细胞的制备和分析; 3） 通过免疫组织化学测定RAR/RXR对转录激活的影响 v-Myb的作用，并且相反，测定v-Myb对 RAR/RXR的转录调控; 4）RAR/RXR的作用分析 5）分析RAR的作用 和RXR对TPA诱导的BM 2细胞分化的影响;和6）鉴定 在Ra处理的BM 2和BM 2-RAR中差异表达的基因 细胞

DESCRIPTION The overall goal of this proposal is to understand the mechanism by which the retinoic acid receptor-a suppresses transformation by the v-Myb oncoprotein. v-Myb transforms monoblasts, macrophage precursors which are blocked in their ability to differentiate. However, the introduction of exogenous RAR-a into the v- Myb-transformed BM2 cell line permits macrophage differentiation in response to retinoic acid, despite the continued presence of the v-Myb protein. Because RAR generally functions as a heterodimer with an RXR protein, the role of RXR proteins in this system is a major focus for the next three-year period. The specific aims for understanding the mechanism by which RAR-a suppresses transformation by v- Myb are the following: 1) Preparation of RXR-a and RXR-a-specific monoclonal antibodies; 2) Preparation and analysis of RXR-a and RXR-a-expressing BM2 cells; 3) Determination of the effect of RAR/RXR on transcriptional activation by v-Myb, and conversely, determination of the effect of v-Myb on transcriptional regulation by RAR/RXR; 4) Analysis of the effect of RAR/RXR upon DNA-binding by v-Myb and vice versa; 5) Analysis of the effect of RAR and RXR upon TPA-induced differentiation of BM2 cells; and 6) Identification of genes which are differentially expressed in Ra treated BM2 and BM2-RAR cells.