Np9 protein of human endogenous retrovirus K interacts with ligand of numb protein X.
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.
Armbruester
Vivienne
V
Department of Virology, University of the Saarland Medical School, D-66421 Homburg/Saar, Germany.
Sauter
Marlies
M
Roemer
Klaus
K
Best
Barbara
B
Hahn
Steffen
S
Nty
Achille
A
Schmid
Andreas
A
Philipp
Stephan
S
Mueller
Anja
A
Mueller-Lantzsch
Nikolaus
N
D000818:Animals; D019556:COS Cells; D002352:Carrier Proteins / Q000378:metabolism*; D002460:Cell Line; D002466:Cell Nucleolus / Q000737:chemistry; D002467:Cell Nucleus / Q000737:chemistry; D002522:Chlorocebus aethiops; D029721:Drosophila Proteins; D020077:Endogenous Retroviruses; D015686:Gene Products, env / Q000378:metabolism*; D006801:Humans; D007605:Juvenile Hormones / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D011485:Protein Binding; D025941:Protein Interaction Mapping; D017434:Protein Structure, Tertiary; D051880:Receptors, Notch; D011994:Recombinant Proteins / Q000378:metabolism; D020798:Two-Hybrid System Techniques; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism
D002352:Carrier Proteins; D029721:Drosophila Proteins; D015686:Gene Products, env; D007605:Juvenile Hormones; D008565:Membrane Proteins; C469430:Np9 protein, HERV-K, human; D051880:Receptors, Notch; D011994:Recombinant Proteins; C060606:numb protein, Drosophila; C484733:LNX1 protein, human; D044767:Ubiquitin-Protein Ligases