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APC mutations disrupt β-catenin destruction complex condensates organized by Axin phase separation.
- Source :
- Cellular & Molecular Life Sciences; Jan2024, Vol. 81 Issue 1, p1-14, 14p
- Publication Year :
- 2024
-
Abstract
- The Wnt/β-catenin pathway is critical to maintaining cell fate decisions. Recent study showed that liquid–liquid-phase separation (LLPS) of Axin organized the β-catenin destruction complex condensates in a normal cellular state. Mutations inactivating the APC gene are found in approximately 80% of all human colorectal cancer (CRC). However, the molecular mechanism of the formation of β-catenin destruction complex condensates organized by Axin phase separation and how APC mutations impact the condensates are still unclear. Here, we report that the β-catenin destruction complex, which is constructed by Axin, was assembled condensates via a phase separation process in CRC cells. The key role of wild-type APC is to stabilize destruction complex condensates. Surprisingly, truncated APC did not affect the formation of condensates, and GSK 3β and CK1α were unsuccessfully recruited, preventing β-catenin phosphorylation and resulting in accumulation in the cytoplasm of CRCs. Besides, we propose that the phase separation ability of Axin participates in the nucleus translocation of β-catenin and be incorporated and concentrated into transcriptional condensates, affecting the transcriptional activity of Wnt signaling pathway. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 1420682X
- Volume :
- 81
- Issue :
- 1
- Database :
- Complementary Index
- Journal :
- Cellular & Molecular Life Sciences
- Publication Type :
- Academic Journal
- Accession number :
- 175122667
- Full Text :
- https://doi.org/10.1007/s00018-023-05068-0