Research article

DWNN, a novel ubiquitin-like domain, implicates RBBP6 in mRNA processing and ubiquitin-like pathways

David JR Pugh¹ , Eiso AB² , Andrew Faro¹ , Portia T Lutya³ , Eberhard Hoffmann⁴ and D Jasper G Rees¹

¹  Biotechnology Department, University of the Western Cape, Modderdam Road, Bellville 7535, South Africa

²  Department of NMR Spectroscopy, Bijvoet Center for Biomolecular Research, University of Utrecht, Padualaan 8, 3584 CH Utrecht, The Netherlands

³  Department of Molecular and Cell Biology, University of the Witwatersrand, 1 Jan Smuts Avenue, Johannesburg 2050, South Africa

⁴  Varian Deutschland GmbH, Alsfelder Straβe 3, D-64289 Darmstadt, Germany

author email corresponding author email

BMC Structural Biology 2006, 6:1doi:10.1186/1472-6807-6-1

Published:	5 January 2006

Abstract

Background

RBBP6 is a 250 kDa splicing-associated protein that has been identified as an E3 ligase due to the presence of a RING finger domain. In humans and mice it interacts with both p53 and Rb, and plays a role in the induction of apoptosis and regulation of the cell cycle. RBBP6 has recently been shown to be highly up-regulated in oesophageal cancer, and to be a promising target for immunotherapy against the disease.

Results

We show here using heteronuclear NMR that the N-terminal 81 amino acids of RBBP6 constitute a novel ubiquitin-like domain, which we have called the DWNN domain. The domain lacks conserved equivalents of K⁴⁸ and K⁶³, although the equivalents of K⁶ and K²⁹ are highly, although not absolutely, conserved. The di-glycine motif that is characteristic of proteins involved in ubiquitination is found in the human and mouse form of the domain, although it is not present in all organisms. It forms part of a three-domain form of RBBP6 containing the DWNN domain, a zinc knuckle and a RING finger domain, which is found in all eukaryotic genomes so far examined, in the majority of cases at single copy number. The domain is also independently expressed in vertebrates as a single domain protein.

Conclusion

DWNN is a novel ubiquitin-like domain found only at the N-terminus of the RBBP6 family of splicing-associated proteins. The ubiquitin-like structure of the domain greatly increases the likelihood that RBBP6 functions through some form of ubiquitin-like modification. Furthermore, the fact that the DWNN domain is independently expressed in higher vertebrates leads us to propose that the domain may itself function as a novel ubiquitin-like modifier of other proteins.