Elucidation for molecular mechanisms of neoplastic cell transformation

细胞周期中G1/S转变的失调有助于肿瘤的发展。c-Jun/c-Myc的降解是G1/S过渡的关键过程。我们发现DYRK2作为一种启动激酶，其c-Jun/c-Myc的磷酸化先于gsk3 β磷酸化，并且是随后gsk3 β磷酸化所必需的。DYRK2沉默缩短了G1期，加速了细胞增殖，因为它们逃避了泛素化介导的降解。EMT在乳腺癌侵袭的早期阶段起着重要的作用。蜗牛是EMT的重要调节器。我们发现DYRK2调节蜗牛的稳定性。在体外和体内，DYRK2的下调促进了EMT和癌症的侵袭。p53 Ser46位点磷酸化可引起细胞凋亡。我们发现双调节蛋白（AREG）是Ser46磷酸化的直接靶点。AREG与DDX5交互。AREG通过DDX5调控前体microRNA加工，降低抗凋亡蛋白Bcl-2的表达。

Dysregulation of the G1/S transition in the cell cycle contributes to tumor development. Degradation of c-Jun/c-Myc is a critical process for the G1/S transition. We found DYRK2 functioning as a priming kinase, whose phosphorylation of c-Jun/c-Myc precedes and is required for subsequent GSK3beta phosphorylation. DYRK2 silencing shortened the G1 phase to accelerate cell proliferation due to their escape from ubiquitination-mediated degradation.EMT plays a fundamental role in the early stages of breast cancer invasion. Snail is an important regulator of EMT. We identified that DYRK2 regulates Snail stability. Knockdown of DYRK2 promoted EMT and cancer invasion in vitro and in vivo.p53 phosphorylation at Ser46 exerts apoptotic cell death. We found that amphiregulin (AREG) is identified for a direct target of Ser46 phosphorylation. AREG interacted with DDX5. AREG regulated precursor microRNA processing with DDX5 to reduce the expression of anti-apoptotic protein Bcl-2.