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Journal of Virology, October 2004, p. 10310-10319, Vol. 78, No. 19
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.19.10310-10319.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Np9 Protein of Human Endogenous Retrovirus K Interacts with Ligand of Numb Protein X

Vivienne Armbruester,¹ Marlies Sauter,¹ Klaus Roemer,¹ Barbara Best,¹ Steffen Hahn,¹ Achille Nty,¹ Andreas Schmid,² Stephan Philipp,³ Anja Mueller,⁴ and Nikolaus Mueller-Lantzsch^1*

Department of Virology,¹ Institute for Physiology,² Institute for Pharmacology and Toxicology, University of the Saarland Medical School, Homburg/Saar, Germany,³ Leukocyte Biology Section, Division of Biomedical Sciences, Faculty of Medicine, Imperial College London, London, United Kingdom⁴

Received 4 February 2004/ Accepted 25 May 2004

We have recently identified Np9 as a novel nuclear protein produced by the human endogenous retrovirus K and were able to document the exclusive presence of np9 transcript in tumors and transformed cells. With the aim of studying whether Np9 has a role in tumorigenesis, a systematic search for interacting proteins was performed. Here, we identify the RING-type E3 ubiquitin ligase LNX (ligand of Numb protein X) as an Np9-interacting partner. We furthermore show that the interaction involves N- and C-terminal domains of both proteins and can affect the subcellular localization of LNX. LNX has been reported to target the cell fate determinant and Notch antagonist Numb for proteasome-dependent degradation, thereby causing an increase in transactivational activity of Notch. We document that LNX-interacting Np9, like Numb, is unstable and degraded via the proteasome pathway and that ectopic Numb can stabilize recombinant Np9. Combined, these findings point to the possibility that Np9 affects tumorigenesis through the LNX/Numb/Notch pathway.

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* Corresponding author. Mailing address: Institute for Medical Microbiology and Hygiene, Department of Virology, Building 47, University of the Saarland Medical School, D-66421 Homburg/Saar, Germany. Phone: 49-6841-1623931. Fax: 49-6841-1623980. E-mail: vinmue{at}med-rz.uni-sb.de.

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Journal of Virology, October 2004, p. 10310-10319, Vol. 78, No. 19
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.19.10310-10319.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

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