Apc | Wnt/β-catenin signaling pathway | CRC

 

好久没有继续我的学习/写作/科普大业了，这个positive feedback loop是非常powerful的。

 

这一期的主题，Apc - Wnt - CRC

这也是我今后的研究主题。

 

先抛出问题：

  • Wnt pathway的组成成分有哪些，都控制了哪些重要的细胞功能？
  • 正常情况下，Apc是如何与Wnt互作的？
  • ApcKO后4-8 day，为何Wnt没有被激活了，什么东西出现了代替了Apc？

 

基本科普：

  • Wnt proteins are secreted morphogens【所以在cellchat里就是个Secreted Signaling的类别】，ligand一般是Wnt.x，而受体则是FZD.x + LRP.x，FZDx的别名就是Frizzled。
  • β-catenin的基因名是CTNNB1，这是一个转录因子coactivator，acts as a coactivator for transcription factors of the TCF/LEF family, leading to activate Wnt responsive genes
  • TCF/LEF, The TCF/LEF family (T cell factor/lymphoid enhancer factor family) is a group of genes that encode transcription factors which bind to DNA through a SOX-like high mobility group domain. They are involved in the Wnt signaling pathway, particularly during embryonic [2] and stem-cell development,[3] but also had been found to play a role in cancer[4] and diabetes.[5] TCF/LEF factors recruit the coactivator beta-catenin to enhancer elements of genes they target.
  • KEGG 的 Wnt signaling pathway - Homo sapiens (human)

其他的非典型Wnt通路

  • The term non-canonical pathway refers to a group of wnt-dependent signalling pathways which do not lead to the cytoplasmic stabilization of soluble β-catenin.
  • Two of these pathways have been well characterized: the planar cell polarity (PCP) and the wnt-Calcium pathway.

 

Wnt通路核心元件

KEGG精细描绘 - https://www.genome.jp/pathway/hsa04310

重点阐述：

  • DVL是第一站的重要中介，一旦ligand+receptor激活，DVL就可以抑制GSK3β的磷酸化活性，β-catenin就自由了，进入细胞核联合CBP等coactivator来配合TCF/LEF家族的TF来激活Wnt通路的靶基因；
  • ligand+receptor未激活时，GSK3β的磷酸化活性就无人（DVL）抑制，其联合AXIN和APC即可将β-catenin磷酸化+泛素化降解，缺乏β-catenin这个核心的coactivator，TCF/LEF家族的TF就无法运转；【CK1a也是降解中的一个重要元件】

 

posted @ 2022-08-05 18:55  Life·Intelligence  阅读(357)  评论(0)  编辑  收藏  举报
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