Elucidation for molecular mechanisms of neoplastic cell transformation

细胞周期中G1/S转换的失调有助于肿瘤的发展。c-Jun/c-Myc的降解是G1/S转换的关键过程。我们发现DYRK 2作为引发激酶发挥作用，其c-Jun/c-Myc的磷酸化先于随后的GSK 3 β磷酸化，并且是随后的GSK 3 β磷酸化所必需的。DYRK 2沉默可缩短G1期，从而加速细胞增殖，使其逃避泛素化介导的降解。EMT在乳腺癌侵袭的早期阶段起着重要作用。Snail是EMT的重要调节因子。我们确定DYRK 2调节Snail稳定性。敲低DYRK 2促进体外和体内EMT和癌症侵袭。p53在Ser 46磷酸化产生凋亡性细胞死亡。我们发现，双调蛋白（AREG）被确定为Ser 46磷酸化的直接靶标。AREG与DDX 5相互作用。AREG通过DDX 5调节前体microRNA加工，以减少抗凋亡蛋白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.