RRC ID 67928
Author Mukai S, Kitazawa R, Ishii J, Kondo T, Hakozaki A, Horiuchi K, Haraguch R, Mori K, Kitazawa S.
Title Identification and analysis of function of a novel splicing variant of mouse receptor activator of NF-κB.
Journal Mol Cell Biochem
Abstract Receptor activator of NF-κB (RANK) is a member of the tumor necrosis factor receptor (TNFR) family expressed in osteoclast precursors, and RANK-RANK ligand (RANKL) signaling is a key system for differentiation, activation and survival of osteoclasts. Here, we report the identification of a novel alternative splicing variant of mouse RANK gene (vRANK) that contains a new intervening exon between exon 1 and exon 2 of mouse full-length RANK (fRANK) mRNA. Since this novel exon contains the stop codon, vRANK encodes truncated amino acids that have a portion of the signal peptide of fRANK and an additional 19 amino acids that show no homology to previously reported domains. By transient transfection studies with vRANK-GFP and -Flag expressing constructs, vRANK was found localized mostly in the cytoplasm and partly in the cell membrane, but was not secreted into the culture supernatant. Under the stimulation of various factors, the expression of vRANK mRNA was almost parallel to that of fRANK in RAW264.7 cells not treated with M-CSF. Overexpression of vRANK, on the other hand, decreased TRACP (a marker of osteoclasts) mRNA expression as well as the number of TRACP-positive multinucleated giant cells. While the mRNA expression levels of NFATc1 (a master transcriptional factor of the osteoclast differentiation program) were not affected, apoptotic cells increased significantly in vRAN K-transfected cells treated with sRANKL. Taken together, these results suggest that vRANK is a novel osteoclast suppressor that reduces the number of RANKL-induced mature osteoclasts mainly by negating the anti-apoptotic effect of RANKL.
Volume 350(1-2)
Pages 29-38
Published 2011-4-1
DOI 10.1007/s11010-010-0679-z
PMID 21153864
MeSH Alternative Splicing / genetics Alternative Splicing / physiology* Animals Apoptosis / genetics Apoptosis / physiology Base Sequence Cell Differentiation / genetics Cell Differentiation / physiology Cells, Cultured Gene Expression Profiling Gene Expression Regulation / physiology Mice Molecular Sequence Data Osteoclasts / metabolism Osteoclasts / physiology Protein Isoforms / analysis Protein Isoforms / genetics Protein Isoforms / physiology RANK Ligand / physiology Receptor Activator of Nuclear Factor-kappa B / chemistry Receptor Activator of Nuclear Factor-kappa B / genetics* Receptor Activator of Nuclear Factor-kappa B / physiology*
IF 2.795
Human and Animal Cells RAW 264(RCB0535)