APC Gene and Wnt/Beta-Catenin Signalling In Cancer Flashcards
What are the phosphorylations that occur for the degradation of beta-catenin
Ser45 - by CKI
Ser 31, 33 and Thr 37 by GSK3Beta
Then ubiquitination by Beta-TrCP
What is TCF bound to in the nucleus that represses it in the absence of Wnt signalling
Bound to the co-repressor Groucho
What % of CRC have APC mutations
80%
The rest usually have beta-catenin mutations
However the 2 are mutually exclusive and do NOT occur together
What Beta-catenin/TCF target genes affect proliferation
Increase; c-myc, cyclin D and COX-2
Repress; PGDH
What Beta-catenin/TCF target genes affect survival
Increase; PPAR, COX-2
Repress: PGDH, p62
What Beta-catenin/TCF target genes affect Differentation
Repress: E-Cadherin
What Beta-catenin/TCF target genes affect migration/invasion
Increase: EphB, MMP7
Repress: Ephrin-B
What Beta-catenin/TCF target genes affect stem cell markers
Increase: LGR5+
Where do most of the mutations occur in Beta-catenin
1285-1515
what are the hot spots for APC mutations
1309 & 1450
What mutant produces the short APC protein
APC1309
What mutatant produces the long APC protein
APC1941
What mutant produces the APC with few polyps but often extra colonic tumours such as desmoid tumours
APC2644
How does LC3 directly interact with Beta-catenin
through the W/YXXI/L motif
What mutations prevent beta-catenin interacting LC3
W504 and 1507
