穿膜蛋白189(Transmembrane protein 189，TMEM189)是本室鉴定的新的细胞自噬相关分子，该基因进化保守，表达广泛，定位于内质网。前期的研究证明，TMEM189在细胞的高表达能够抑制饥饿或Rapamycin诱导的自噬，敲减TMEM189则能够增加常态以及应激状态的细胞自噬。进一步的研究证明TMEM189能够与ULK1相互作用，促进ULK1的衰变，增加其不稳定性，证明TMEM189可能通过靶向ULK1信号通路负向调控自噬。本课题拟在前期研究的基础上，进一步利用多种分子细胞生物学技术，结合Tmem189基因敲除小鼠以及肿瘤动物模型等，系统阐述TMEM189在正常和应激状态下调控自噬过程的分子机制，证明TMEM189-ULK1信号通路在维持自噬稳态中的作用以及病理生理意义。这些研究成果的取得，有望为复杂的自噬网络调控提供新的内容，具有重要的理论意义和潜在的应用价值。

Transmembrane protein 189 (TMEM189) was first identified as a novel human gene related with autophagy in our laboratory. The gene is evolutionarily conserved and widely expressed. It is localized to the endoplasmic reticulum. Our previous studies have shown that the overexpression of TMEM189 can inhibit starvation- or Rapamycin-induced autophagy, while knockdown of TMEM189 can increase autophagy with the steady and stress state. Further studies have shown that TMEM189 can interact with ULK1, promote the decay of ULK1 and increase its instability, suggesting that TMEM189 may negatively regulate autophagy by targeting ULK1 signaling pathway. On the basis of previous studies, this subject intends to further elaborate the molecular mechanism of TMEM189-regulating autophagy in normal and stressed states by using various molecular cell biology techniques, combined with Tmem189 gene knockout mice and tumor animal models. We will further demonstrate the role of TMEM189-ULK1 signaling pathway in maintaining autophagy homeostasis and its pathophysiological significance. These achieved results are expected to provide new content for the complex autophagy regulatory network and have important theoretical significance and potential application value.