Myc/Max/Mad网络作为重要的转录因子轴，在维持细胞生长，增殖，凋亡，分化及能量代谢等一系列生物学功能方面起着重要的调节作用。而作为Myc抑制蛋白的Mxi1被认为是一种潜在的抑癌基因，通过抑制Myc的转录活性发挥其功能，但其调控机制目前尚不明确。本研究前期结果发现：活化型而非失活型的S6K1(RPS6KB1)激酶能导致Mxi1的降解，其蛋白表达水平下调，且Mxi1 Serine160可能是S6K1潜在的磷酸化位点。免疫沉淀实验发现S6K1和Mxi1存在相互作用。因此，本研究将进一步从分子水平探求Mxi1被S6K1磷酸化而影响其稳定性，进而影响其功能的机理。同时, 研究S6K1和Mxi在乳腺癌中的临床意义及两者的相关性。本研究的完成，可以从机理上阐明Mxi1是如何被调控从而影响Myc的转录活性，并为乳腺癌研究提供新的分子靶标。

Myc/Max/Mad network, a critical transcriptional factor axis, plays essential roles in diverse biological processes such as cell growth, proliferation, apoptosis, differentiation, cell metabolism and so on. Myc inhibitory protein Mxi1 is regarded as a candidate tumor suppressor gene, and serves many functions by inhibiting transcriptional activity of Myc. However, the regulatory mechanisms of Mxi1 are unclear.Our preliminary data show constitutively active (CA) but not kinase-dead (KD) S6K1 (RPS6KB1) leads to the degradation and downregulation of Mxi1, and Serine160 on Mxi1 is a potential phosphorylation site.co-IP assay shows S6K1 binds to Mxi1. Therefore, this project intends to uncover:1) S6K1 phosphorylates Mxi1 in vitro and in vivo, 2) this phosphorylation influences the stability of Mxi1,3)this phosphorylation affects some functions of Mxi1,4)the clinical significance and correlation of S6K1 and Mxi1 in breast cancer.This study will demonstrate that how Mxi1 is regulated mechanistically in cells，and provide a novel molecular target for breast cancer.