Structural and Functional Characterization of the RAI2 Protein

在大多数癌症患者中，死亡率与转移有关。在我们正在进行的DFG资助的UKE项目(DFG 5/2012-4/2015)中，维甲酸诱导的2(RAI2)基因在原发乳腺肿瘤中的表达缺失被鉴定为一种新的基因决定因素，尤其与激素受体阳性乳腺肿瘤的不良预后和早期转移相关。为了开始RAI2蛋白的功能表征，在EMBL的汉堡单位与Wilmanns小组开始了科学合作。UKE和EMBL的研究团队的这些共同努力使人们首次深入了解了RAI2蛋白以前完全未知的功能。我们能够证明RAI2蛋白可以作为转录辅助调节因子，支持腔内乳腺癌细胞的分化，从而导致更具侵袭性的肿瘤细胞表型。在提出的研究项目中，我们希望通过分析RAI2蛋白的相互作用组和分子结构来继续我们成功的合作，并深化RAI2蛋白的功能表征。这将有助于实现我们的长期目标，即探索RAI2蛋白是否可以代表可用于开发新的治疗策略或增强现有治疗癌症患者的治疗策略的可药物靶点。

In most cancer patients, mortality is linked to metastasis. In the course of our proceeding DFG-funded project at UKE (DFG 5/2012-4/2015) loss of retinoic acid-induced 2 (RAI2) gene expression in primary breast tumors was indentified as a novel genetic determinant associated especially with poor prognosis and early metastatic spread of hormone receptor positive breast tumours. To start the functional characterization of the RAI2 protein, scientific collaboration was initiated with the Wilmanns group at the Hamburg unit of the EMBL. These joint efforts of the research teams at UKE and EMBL led to first insight into the previously completely uncharacterized functions of the RAI2 protein. We were able to show that the RAI2 protein can act as a transcriptional co-regulator that sustains the differentiation of luminal breast cancer cells, which leads to a more aggressive phenotype of tumor cells. In the proposed research project, we want to continue our successful collaboration and deepen the functional characterization of the RAI2 protein by analyzing the interactome and the molecular structure of this still poorly characterized protein. This will help to approach our long-term goal to explore whether the RAI2 protein could represent a drugable target for the development of novel therapeutic strategies or for the enhancement of existing ones for the treatment of cancer patients.