Frameshift and missense mutations have been identified in th...

created [InstanceEdit:5340531] Rothfels, K, 2014-03-19
dbId 5340530
displayName Frameshift and missense mutations have been identified in th...
modified [InstanceEdit:5545643] Rothfels, Karen, 2014-05-22
schemaClass Summation
text Frameshift and missense mutations have been identified in the E3 ubiquitin ligase RNF43 in pancreatic and colorectal cancers, and these trucated, loss of function proteins are believed to be inactive (Ivanov et al, 2007; Koo et al, 2012; Jiang et al, 2013). In wild type cells, RNF43 and the related ZNRF3 protein play a role in down-regulating WNT signaling by ubiquitinating the FZD receptors and promoting their internalization; RNF43 and ZNRF3 are also WNT-target genes, establishing a negative feedback loop (Hao et al, 2012; Mukai et al, 2010; Yagyu et al, 2004; van der Flier et al, 2007). Cells depleted of RNF43 or expressing an oncogenic frameshift mutant are dependent upon stimulation by secreted WNT ligand for their proliferation. Consistent with this, treatment with the Porcupine inhibitor LGK974, which traps WNT in the ER, abrogates the growth of these cells (Koo et al, 2012; Jiang et al, 2013). Depletion of RNF43 results in elevated levels of FZD receptors in the cell membrane and increased expression of WNT reporters and endogenous target genes (Koo et al, 2012; Jiang et al, 2013).
Cite Us!