Sumoylation of Daxx Regulates Ifn-induced Growth Suppression of B Lymphocytes and the Hormone Receptor-mediated Transactivation.
From: Department of Immunology, Graduate School of Pharmaceutical Sciences, Hokkaido University, Kita-Ku, Kita 12 Nishi 6, Sapporo 060-0812, Japan.
Journal of immunology (Baltimore, Md. : 1950)
- Publish Date: Jul 2006
- ISSN: 0022-1767
- Volume: 177
- Issue: 2
- Pages: 1160-70
- Medium: Print
- Language: English
- Citation (JAMA): Muromoto Ryuta, Ishida Masato, Sugiyama Kenji, et al. Sumoylation of Daxx Regulates Ifn-induced Growth Suppression of B Lymphocytes and the Hormone Receptor-mediated Transactivation.. J. Immunol. Jul 2006;177:1160-70
Abstract
Daxx has been shown to play an essential role in type I IFN-mediated suppression of B cell development and apoptosis. Recently, we demonstrated that Tyk2 is directly involved in IFN signaling for the induction and translocation of Daxx, which may result in growth arrest and/or apoptosis of B lymphocyte progenitors. To clarify the molecular mechanisms of how Daxx acts on growth suppression of B lymphocytes, we examined functions of a sumoylation-defective Daxx KA mutant (Daxx K630/631A), which substituted Lys 630 and Lys 631 to Ala. Importantly, Daxx KA localized in the cytoplasm, whereas wild-type Daxx localized in the nucleus. Murine pro-B cell line Ba/F3 expressing Daxx KA revealed a resistance to the IFN-induced growth suppression. It is noteworthy that treatment with an exportin inhibitor, leptomycin B, resulted in nuclear localization of Daxx KA and recovery of the IFN-induced growth suppression in Ba/F3 cells. Moreover, Daxx KA decreased the binding potential to promyelocytic leukemia protein (PML), and overexpression of PML recruited Daxx KA into PML oncogenic domains. Notably, a Daxx-small ubiquitin-related modifier fusion protein exhibited increased nuclear localization and ability to suppress cell growth in Ba/F3 cells. These results demonstrate that the IFN-induced growth suppression of B lymphocytes requires nuclear localization of Daxx through its sumoylation and proper interactions with PML.
Mesh Headings (Keywords): Active Transport, Cell Nucleus, Alanine, Amino Acid Substitution, Animals, B-Lymphocytes, Carrier Proteins, Cell Line, Cell Line, Tumor, Cytoplasm, Growth Inhibitors, Hela Cells, Humans, Interferons, Intracellular Signaling Peptides and Proteins, Lysine, Mice, Neoplasm Proteins, Nuclear Proteins, Receptors, Glucocorticoid, Small Ubiquitin-Related Modifier Proteins, Trans-Activation (Genetics), Transcription Factors, Tumor Suppressor Proteins, Ubiquitin-Conjugating Enzymes, Up-Regulation
Check for Full Text / PubMed Unique Identifier (PMID): 16818774
This abstract is part of PubMed, a service of the U.S. National Library of Medicine. PubMed includes more than 17 million citations from MEDLINE and other life science journals for biomedical articles. See Copyright and Disclaimers.
Linked medical terms appearing on this page are added by Healia to help readers find more information and are not part of the original PubMed document.
The data herein was last updated on July 8th, 2008 and may not reflect the most current and accurate data available from NLM.