Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.


Logo for

Genes & Dev. 26 (3): 235-240

Copyright © 2012 by Cold Spring Harbor Laboratory Press.


Recognition of the iso-ADP-ribose moiety in poly(ADP-ribose) by WWE domains suggests a general mechanism for poly(ADP-ribosyl)ation-dependent ubiquitination

Zhizhi Wang1,2, Gregory A. Michaud3, Zhihong Cheng1, Yue Zhang3, Thomas R. Hinds4, Erkang Fan1,5, Feng Cong3,, and Wenqing Xu1,6

1 Department of Biological Structure,
2 Biomolecular Structure and Design Program, University of Washington, Seattle, Washington 98195, USA;
3 Novartis Institutes for Biomedical Research, Cambridge, Massachusetts 02139, USA;
4 Department of Pharmacology,
5 Department of Biochemistry, University of Washington, Seattle, Washington 98195, USA

Abstract: Protein poly(ADP-ribosyl)ation and ubiquitination are two key post-translational modifications regulating many biological processes. Through crystallographic and biochemical analysis, we show that the RNF146 WWE domain recognizes poly(ADP-ribose) (PAR) by interacting with iso-ADP-ribose (iso-ADPR), the smallest internal PAR structural unit containing the characteristic ribose–ribose glycosidic bond formed during poly(ADP-ribosyl)ation. The key iso-ADPR-binding residues we identified are highly conserved among WWE domains. Binding assays further demonstrate that PAR binding is a common function for the WWE domain family. Since many WWE domain-containing proteins are known E3 ubiquitin ligases, our results suggest that protein poly(ADP-ribosyl)ation may be a general mechanism to target proteins for ubiquitination.

Key Words: poly(ADP-ribosyl)ation • ubiquitination • WWE domain • PARP-1 • axin • crystal structure

Received for publication November 2, 2011. Accepted for publication December 19, 2011.

6 Corresponding author.

E-mail wxu{at}

Supplemental material is available for this article.

Article published online ahead of print. Article and publication date are online at

The FHA and BRCT domains recognize ADP-ribosylation during DNA damage response.
M. Li, L.-Y. Lu, C.-Y. Yang, S. Wang, and X. Yu (2013)
Genes & Dev. 27, 1752-1768
   Abstract »    Full Text »    PDF »
Celebrating 30 Years of Wnt Signaling.
F. Verkaar, K. M. Cadigan, and R. van Amerongen (2012)
Science Signaling 5, mr2
   Abstract »    Full Text »    PDF »
Quantitative proteomics profiling of the poly(ADP-ribose)-related response to genotoxic stress.
J.-P. Gagne, E. Pic, M. Isabelle, J. Krietsch, C. Ethier, E. Paquet, I. Kelly, M. Boutin, K.-M. Moon, L. J. Foster, et al. (2012)
Nucleic Acids Res. 40, 7788-7805
   Abstract »    Full Text »    PDF »
GDP-Mannose-4,6-Dehydratase Is a Cytosolic Partner of Tankyrase 1 That Inhibits Its Poly(ADP-Ribose) Polymerase Activity.
K. K. Bisht, C. Dudognon, W. G. Chang, E. S. Sokol, A. Ramirez, and S. Smith (2012)
Mol. Cell. Biol. 32, 3044-3053
   Abstract »    Full Text »    PDF »

To Advertise     Find Products

Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882