Abstract
Human PRUNE is thought to enhance the metastasis of tumor cells. We found that a hypothetical paralog of PRUNE, PRUNE2, binds to 8-oxo-GTP, an oxidized form of GTP. Hypothetical PRUNE2 gene consists of C9orf65 and BMCC1/BNIPXL, both of which are malignant tumor-associated genes. We isolated PRUNE2 complementary DNA and revealed that the protein is composed of 3,062 residues. C9orf65 and BMCC1/BNIPXL encode the N-terminal part (259 residues) and C-terminal part (2,729 residues) of PRUNE2, respectively. We demonstrated the endogenous full-length PRUNE2 protein (338 kDa) by Western blot and mass spectrometry. PRUNE2 bound to 8-oxo-GTP as well as GTP. The expression levels of human PRUNE2 and mouse Prune2 messenger RNA (mRNA) were highest in the dorsal root ganglia (DRG) and, to a lesser extent, in other nerve tissues. DRG neurons express higher levels of PRUNE2 in their soma compared with adjacent cells. In addition, their expression levels in the adult nerve tissues were higher than those in fetal or neonatal nerve tissues. The present study indicates that C9orf65 and BMCC1/BNIPXL are transcribed as PRUNE2 mRNA, which is translated to a large PRUNE2 protein. The nerve tissue-specific and post-development expression of PRUNE2/Prune2 suggests that PRUNE2 may contribute to the maintenance of mature nervous systems.
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Acknowledgments
We thank Dr. Toru Iwaki for providing human tissue samples and helpful discussion. We thank Dr. Masaki Matsumoto from the Division of Proteomics of the Medical Institute of Bioregulation for helpful discussions. We thank Mizuho Oda, Emiko Koba, and Masumi Ohtsu from the Laboratory for Technical Support of the Medical Institute of Bioregulation and Setsuko Kitamura and Kazumi Asakawa for their technical assistance. This work was supported by MEXT KAKENHI 20013034, 21117512, JSPS KAKENHI 19390114, and by the Kyushu University Global COE program. T.I. is a research fellow of JSPS.
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Oligonucleotides used in this study (DOC 29 kb)
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Iwama, E., Tsuchimoto, D., Iyama, T. et al. Cancer-Related PRUNE2 Protein Is Associated with Nucleotides and Is Highly Expressed in Mature Nerve Tissues. J Mol Neurosci 44, 103–114 (2011). https://doi.org/10.1007/s12031-010-9490-2
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DOI: https://doi.org/10.1007/s12031-010-9490-2