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J. Biol. Chem., Vol. 276, Issue 22, 19238-19243, June 1, 2001

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rDRAK1, a Novel Kinase Related to Apoptosis, Is Strongly Expressed in Active Osteoclasts and Induces Apoptosis^*

Hiroko Kojima^§¶, Atsuko Nemoto^§, Toshimasa Uemura^§**, Reiko Honma^§, Mariko Ogura^§§§, and Yin-kun Liu^¶¶

From the ^§ Tissue Engineering Research Center (TERC), National Institute of Advanced Industrial Science and Technology (AIST), 1-1-1 Higashi, Tsukuba Ibaraki 305-8562, Japan,  CREST Japan Science and Technology Corporation (JST), 4-1-8 Honcho Kawaguchi, Saitama 332-0012, Japan, ^** Department of Biomedical Engineering, Graduate School of Medicine, University of Tokyo, 7-3-1, Hongo, Bunkyoku, Tokyo 113-0033, Japan, ^§§ Institute of Applied Biochemistry, University of Tsukuba, Tsukuba Ibaraki, 305-8572, Japan, and ^¶¶ Liver Cancer Institute, Shanghai Medical University, Yi Xue-Yuan Road, Shanghai 200032, China

This is the first report of a novel serine/threonine kinase, rabbit death-associated protein (DAP) kinase-related apoptosis-inducing protein kinase 1 (rDRAK1), involved in osteoclast apoptosis. We searched for osteoclast-specific genes from a cDNA library of highly enriched rabbit osteoclasts cultured on ivory. One of the cloned genes has a high homology with human DRAK1 (hDRAK1), which belongs to the DAP kinase subfamily of serine/threonine kinases. By screening a rabbit osteoclast cDNA library and 5'-RACE (rapid amplification of cDNA ends), we obtained a full length of this cDNA, termed rDRAK1. The sequencing data indicated that rDRAK1 has 88.0, 44.6, 38.7, and 42.3% identity with hDRAK1, DAP kinase, DRP-1, and ZIP (zipper-interacting protein) kinase, respectively. To clarify the role of DRAK1 in osteoclasts, we examined the effect of three osteoclast survival factors (interleukin-1, macrophage colony-stimulating factor, and osteoclast differentiation-inducing factor) on rDRAK1 mRNA expression and the effect of rDRAK1 overexpression on osteoclast apoptosis. The results suggested that these three survival factors were proved to inhibit rDRAK1 expression in rabbit osteoclasts. After transfection of a rDRAK1 expression vector into cultured osteoclasts, overexpressed rDRAK1 was localized exclusively to the nuclei and induced apoptosis. Hence, rDRAK1 may play an important role in the core apoptosis program in osteoclast.

The nucleotide sequence(s) reported in this paper has been submitted to the GenBank^TM/EMBL Data Bank with accession number(s) AB042195 (rDRAK1).

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