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Endonuclein is a cell cycle regulated WD-repeat protein that is up-regulated in adenocarcinoma of the pancreas

Abstract

The transcript encoding endonuclein, the human homolog of yeast PWP1, was previously found up-regulated in pancreatic cancer tissue. By immunohistochemistry we detected a ubiquitous presence in several tissues examined: skin, liver, thyroid gland, heart muscle, neurons, kidney, bladder, pancreas, adrenal gland, ovary, uterus, testis and prostate gland. We especially noticed that normal pancreatic exocrine cells exhibited low protein levels while pancreatic adenocarcinoma cells revealed high levels. We found a heterogeneous subcellular distribution, especially with varying nuclear levels. In proliferating cells endonuclein protein expression and localization was cell cycle dependent, with increasing levels and nuclear focusing during the interphase toward mitosis. Ultrastructural analysis revealed ER and nuclear localization. Endonuclein contains five WD-repeats, indicating a putative role in crucial regulatory activities in the nucleus as well as in the ER.

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Abbreviations

ER:

endoplasmic reticulum

GST:

glutathion S-transferase.

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Acknowledgements

We thank Inge Kjærgaard, Kirsten Peterslund, and Zhila Nikrozi for expert technical assistance. This work was supported by grants from the Danish Medical Research Council, the Novo Nordisk Foundation, Grosserer Valdemar Foersom og hustru Thyra Foersom, født Otto's Fond, Fru Astrid Thaysens Legat for Lægevidenskabelig Grundforskning and the Karen Elise Jensen Foundation.

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Correspondence to Bent Honoré.

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Honoré, B., Baandrup, U., Nielsen, S. et al. Endonuclein is a cell cycle regulated WD-repeat protein that is up-regulated in adenocarcinoma of the pancreas. Oncogene 21, 1123–1129 (2002). https://doi.org/10.1038/sj.onc.1205186

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