Question

can you help solve problems 6-9?

Assignment: The Wnt/ ß-catenin pathway Inn Inn TUTTI I Fzd www Plasma membrane LRP 1100Fzd UVU DSH C DSH Ubiquitin-mediated degradation B.catenin B-catenin Min Note: GSK3, APC and Axin together are called the B-catenin Destruction Complex DSH is the abbreviation for Dishevelled. The human genome encodes many Fzd receptors, several Dsh proteins, one GSK3, and one ß-catenin. Questions 1. What are the components of the receptor complex? What is the ligand? 2. What is the molecular function of ß-catenin itself? 3. Where is ß-catenin found within the cell? Does its subcellular location ever change? 4. What are the molecular functions of GSK3, APC, and Axin? 5. Define proteolysis. 6. Describe the ultimate outcome of Wnt pathway activation. 7. Give two examples of negative regulation found here. Contrast their molecular mechanisms. 8. Describe the effect of loss-of-function mutations in Frizzled, DSH, GSK3, and B-catenin separately on the transcription of target genes. You can assume that mutations in any part of the B-catenin Destruction Complex will cause the loss of function of the entire complex. 9. What would be the result of a double knock-out of DSH and APC? Of GSK3 and B-catenin?

Answer 1

Okay, six and nine.

6.- For this you have to be aware of what Wnt pathway leads to. This pathway prevents beta-cetenin from being degraded, then it can go to the nucleus (at high concentrations in cytoplasm) and, along with other transcription factors, regulate gene transcription. So the final outcome is a different behavior in transcription activity in the nucleus, certain needed transcribed genes. The effect of high concentrations of beta-catenin leads to overexpression.

9.- Now consider scenarios where:

- There are no DSH nor APC. So now, APC is part of the destruction complex that degrades beta catenin, this molecule attaches to beta-catenin so it can get ubiquitinated to get degraded. A lack of APC makes impossible for the cell to degrade beta-catenin. DSH activates the Wnt pathway, it inhibits the action of the destruction complex, leading to evade beta-catenin degradation.

This means this scenario would lead to pretty high levels of beta-catenin, leading to overexpression in the cell.

- There are no GSK3 nor Beta-catenin. The GSK3 molecule is part of the destruction complex, a lack of it will stop the beta-catenin degradation, but we don't have beta-catenin in this scenario either, so there is nothing to do anyway. In this scenario there is just no way of reaching the transcription activation effect that beta-catenin produces. The cell stays without such influence. The action of Wnt pathway would be useless as there is no catenin to protect.