Ubiquitin Ligase RNF146 Regulates Tankyrase and Axin to Promote Wnt Signaling
2011

RNF146 Regulates Wnt Signaling by Destabilizing Axin and Tankyrase

Sample size: 653 publication 10 minutes Evidence: moderate

Author Information

Author(s): Callow Marinella G., Tran Hoanh, Phu Lilian, Lau Ted, Lee James, Sandoval Wendy N., Liu Peter S., Bheddah Sheila, Tao Janet, Lill Jennie R., Hongo Jo-Anne, Davis David, Kirkpatrick Donald S., Polakis Paul, Costa Mike

Primary Institution: Genentech Research and Early Development, South San Francisco, California, United States of America

Hypothesis

RNF146 is a positive regulator of Wnt signaling that operates with tankyrase to maintain low levels of Axin proteins.

Conclusion

The study identifies RNF146 as a key regulator of Wnt signaling through its role in the degradation of Axin and tankyrase proteins.

Supporting Evidence

  • RNF146 was identified as a positive regulator of Wnt signaling through RNAi screening.
  • Knockdown of RNF146 resulted in increased levels of Axin proteins.
  • RNF146 was shown to mediate the ubiquitylation of tankyrase and Axin.

Takeaway

This study found that a protein called RNF146 helps control a signaling pathway important for cell growth and development by breaking down other proteins that would stop this signaling.

Methodology

The researchers conducted RNAi screening in HEK293 cells to identify genes that regulate Wnt signaling and analyzed the effects of RNF146 on Axin and tankyrase protein levels.

Potential Biases

The authors are affiliated with Genentech, which may introduce bias in the interpretation of results.

Limitations

The study does not explore the role of RNF146 in all cell types or its potential effects in vivo.

Digital Object Identifier (DOI)

10.1371/journal.pone.0022595

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