Poster Presentation 26th Lorne Cancer Conference 2014

Coordinating multiple APC tumour suppressor activities with non-proteolytic ubiquitin chains (#270)

Hoanh Tran 1 , Paul Polakis 2
  1. Ludwig Institute for Cancer Research, Melbourne, VIC, Australia
  2. Genentech, Inc., South San Francisco, CA, USA

Colon cancer is a leading cause of cancer mortality in western societies. In the vast majority of cases, initiation of colon cancer development is caused by mutations that inactivate the APC tumour suppressor gene. APC protein has two established cellular functions. First, it suppresses Wnt signalling, a growth-promoting pathway that is over-activated in nearly all colon cancers. Second, APC promotes directional cell migration. How these two tumour suppressor functions of APC are coordinated to control cell growth and migration is not known. We recently discovered that APC is modified with non-proteolytic ubiquitin chains, and several observations indicate that this novel modification could link the two functions of APC in Wnt signalling and cell migration1-4. We will discuss implications of APC ubiquitin modification with respect to the function of truncated APC proteins frequently observed in colon cancer.

  1. Tran, H*. & Polakis, P*. (2012) Reversible modification of adenomatous polyposis coli (APC) with K63-linked polyubiquitin regulates the assembly and activity of the beta-catenin destruction complex. JBC 287, 28552-28563. *Corresponding author.
  2. Tran, H*., et al. (2013) HectD1 E3 ligase modifies adenomatous polyposis coli (APC) with polyubiquitin to promote the APC-axin interaction. JBC 288, 3753-3767. *Corresponding author.
  3. Tran, H., Hamada, F., Schwarz-Romond, T., & Bienz, M. (2008) Trabid, a new positive regulator of Wnt-induced transcription with preference for binding and cleaving K63-linked ubiquitin chains. Genes & Dev 22, 528-542.
  4. Tran, H., & Polakis, P. Unpublished.