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Metastatic Lymph Node 51, a novel nucleo-cytoplasmic protein overexpressed in breast cancer

Abstract

Metastatic Lymph Node 51 (MLN51) cDNA was isolated by differential screening of a human breast cancer metastasis cDNA library. MLN51 cDNA encodes a novel human protein of 703 residues that shares no significant homology to any known protein. However MLN51 is well conserved between vertebrate and invertebrate species suggesting an important biological function. The amino terminal half of the protein contains a coiled-coil domain and two potential nuclear localization signals (NLS). The carboxy terminal half contains one SH2 and four SH3 binding motifs. The coiled-coil domain promotes MLN51 oligomerization in transfected cells. When transiently expressed, the MLN51 protein is mainly found in the cytoplasm with a weak nuclear staining. However, deletion of the carboxy terminal half of the protein allows the targeting of the protein to the nucleus, demonstrating that the NLSs are functional. MLN51 is ubiquitously expressed in normal tissues. Human breast carcinomas show MLN51 overexpression in malignant epithelial cells. The uncommon association of protein–protein interaction domains often found either in nuclear or in cytoplasmic signaling proteins raises a possible nucleo-cytoplasmic function for MLN51.

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Acknowledgements

The authors thank S Chan for critical reading of the manuscript; G Duval, P Eberling, I Stoll, M Gintz for technical assistance; F Alpy, for helpful discussions. This work was supported by funds from the Institut National de la Santé et de la Recherche Médicale, Centre National de la Recherche Scientifique, Hôpital Universitaire de Strasbourg, the Association pour la Recherche sur le Cancer, the Ligue Nationale Française contre le Cancer (LNCC), the LNCC Comités du Haut-Rhin et du Bas-Rhin and the Fondation de France. S Degot was a recipient of an Allocation du Ministère de l'Education Nationale, de la Recherche et de la Technologie.

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Correspondence to Catherine Tomasetto.

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Degot, S., Régnier, C., Wendling, C. et al. Metastatic Lymph Node 51, a novel nucleo-cytoplasmic protein overexpressed in breast cancer. Oncogene 21, 4422–4434 (2002). https://doi.org/10.1038/sj.onc.1205611

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