Regulation of c-myc translation by hnRNP A1: Role in multiple myeloma tumor responses

这个项目的主要目标是为未来c-myc IRES的治疗靶向提供理论基础。 它在多发性骨髓瘤细胞中介导帽非依赖性翻译。依赖于IRES的myc翻译是 在这个肿瘤模型中，内质网应激对肿瘤细胞的存活至关重要。目的包括研究这种机制。 MNK激酶、hnRNP A1 ITAF和核糖体蛋白RPS25通过其介导IRES功能； Myc诱导A1和RPS25表达的机制和重要性及其作为一种潜在的抑制因子的可能性 IRES在骨髓瘤中发挥作用。骨髓瘤细胞的存活与死亡及其实现c-myc的能力 翻译和IRES的体外活性将被研究。此外，c-myc驱动的小鼠骨髓瘤模型将 被用来确定hnRNPA1和IRES活性在肿瘤进展中的体内作用以及 我们的IRES抑制剂的潜在疗效。

The main objective of this project is to provide a rationale for future therapeutic targeting of the c-myc IRES which mediates cap-independent translation in multiple myeloma cells. IRES-dependent myc translation is critical for tumor cell survival during ER stress in this tumor model. The aims include studying the mechanism by which the MNK kinase, the hnRNP A1 ITAF and the ribosomal protein RPS25 mediate IRES function; the mechanism and importance of myc inducing A1 and RPS25 expression and the potential for an inhibitor of IRES function in myeloma. The viability versus death of myeloma cells as well as their ability to achieve c-myc translation and IRES activity in vitro will be studied. In addition, a murine model of c-myc-driven myeloma will be exploited to determine the in vivo roles of hnRNPA1 and IRES activity in tumor progression as well as the potential efficacy of our IRES inhibitors.