The following is a thought-experiment. b-catenin is a cytoplasmic protein that a

Question

The following is a thought-experiment. b-catenin is a cytoplasmic protein that associates with the cytoplasmic domain of cadherins. It can also transit into the nucleus to alter gene expression. Excessive b-catenin signaling in the nucleus sets the stage for disease, like progression towards cancer. Consider a mutant cell that no longer expresses E-cadherin but otherwise has no other mutations. Does this cell experience unregulated, constitutive b-catenin signaling in the nucleus? Please explain, but keep it brief (a couple of sentences should suffice).

Explanation / Answer

Although gain- and loss-of-function experiments clearly demonstrate that cadherin levels can affect -catenin signaling, the notion that cadherin loss is sufficient to promote -catenin signaling by releasing it from the cadherin-bound pool is largely incorrect This is because although a cadherin can bind a newly synthesized -catenin, compete for its association with the Axin/APC degradation complex, and stabilize it, cadherin loss appears to let this process work in reverse, allowing the once cadherin-bound -catenin to be consumed by the degradation machinery. Simply, loss of the cadherin alone does not increase -catenin stabilization and signaling when the degradation pathway is intact. It is perhaps most accurate to consider that E-cadherin sets a threshold for Wnt/-catenin signaling: high cadherin expression—as is typically found in epithelial tissues—serves to keep Wnt signals off, whereas cadherin loss can potentiate Wnt signaling driven at many points in the pathway. There are, though, additional levels of complexity. Some intriguing studies revealed that cadherin-mediated cell–cell adhesion and polarity (rather than changes in cadherin expression) may affect the strength or duration of Wnt/-catenin signals through a poorly defined mechanism.

Related Questions

Navigate

• Browse (All)
• Browse T
• Subjects

Integrity-first tutoring: explanations and feedback only — we do not complete graded work. Learn more.