Transcriptional regulation of RACK1 and modulation of its expression: Role of steroid hormones and significance in health and aging.

The Receptor for Activated C Kinase 1 (RACK1) is a scaffold protein for different kinases and membrane receptors. RACK1 can shuttle proteins to their sites of action, facilitate cross-talk among distinct signaling pathways or recruit other signaling proteins into the complexes. Therefore, it is a key mediator of various pathways and is involved in various biological events including development, immune response, brain activity and cancer. Because of its importance, it is of extreme significance to understand the transcriptional mechanisms governing its expression. The identification of regulatory elements in the promoter of RACK1 shed some light on its transcriptional modulation in physiological and pathological context. Literature data support the existence of a complex hormonal balance, between glucocorticoids and androgens, in the control of RACK1 expression due to specific and complex interactions on the RACK1 promoter. These and other informations suggest that a better understanding of RACK1 transcriptional regulation is essential to unravel its role. Furthermore, the modulation of its expression in physiological or pathological conditions may be of interest in different context, such as aging and cancer.

Effect of receptor for activated C kinase 1 gene silencing on the sensitivity of cell line A549 to chemotherapeutic drugs / 肿瘤研究与临床

Objective To investigate the effect of shRNA-mediated down-regulation of the receptor for activated C kinase 1 (RACK1) gene on the chemotherapeutic sensitivities in human lung adenocarcinoma cell line A549.Methods The shRNA recombinant plasmid targeting to human RACK1 gene was designed and transferred into A549 cells by lipofectin technique.The protein level of RACK1 was measured by Western blot to confirm the function of shRNA plasmid.Drug sensitivities of A549 cells to cisplatin,gemcitabine,pemetrexed and paclitaxel were analyzed by MTT assay.The protein expression of LRP and MRP were detected by Western blot.Results After 24 hours transfection,the relative expression quantity of RACK1 protein in RACK1-shRNA group was 0.267± 0.470,which was significantly lower than that in vector-shRNA group (0.821±0.109) and control group (0.842±0.060) (F =54.438,P ＜ 0.05).The results of MTT showed that the growth of A549 cells in the RACK1-shRNA group was markedly inhibited.The sensitivities of A549 cells to cisplatin and paclitaxel were significantly enhanced compared with that in the vector-shRNA group and control group (P ＜ 0.05).The relative expression quantity of LRP and MRP protein in RACK1-shRNA group were 0.163±0.056 and 0.246±0.050,which were lower than that in vector-shRNA group and control group (F LRP =19.430,F MRP =61.548,both P ＜ 0.05).Conclusion Targeted gene silencing of RACK1 improves the sensitivity of A549 cells to the ascisplatin and paclitaxel medicines,which might be achieved through down-regulation of the expression of LRP and MRP.