International Immunology, Vol 10, 203-210, Copyright © 1998 by Oxford University Press
R Horie, S Aizawa, M Nagai, K Ito, M Higashihara, T Ishida, J Inoue and T Watanabe
About 100 amino acid residues in the C-terminal region are conserved among
human, rat and murine CD30, a member of the tumor necrosis factor receptor
(TNFR) superfamily, and can be separated into three subdomains with
relatively higher conservation (D1, D2 and D3). Activation of NFkappaB by
CD30 was shown to be mediated through interaction of TNFR- associated
factor (TRAF) 1, 2 and 5 with the D2 and D3 subdomains. However, the
function of the other conserved subdomain, D1, remained to be determined.
Deletion of the D2 and D3 subdomains abolished interactions with TRAF2 and
5 but it did not affect NFkappaB activation. Reporter gene assays using
deletion and mutant constructs of CD30 revealed that the D1 subdomain is
sufficient for NFkappaB activation, without interaction with TRAF2 or 5,
and that each subdomain alone can activate NFkappaB. Electrophoretic
mobility shift assays revealed constitutive and CD30-induced NFkappaB
activation in stable transformants of 293 cells expressing CD30 or a
deletion mutant lacking D2 and D3 subdomains. Deletion of C-terminal 19
amino acid residues of the D1 subdomain abolished activation of NFkappaB.
Substitution of alanine for one of the two threonine residues (amino acid
position 524 and 529), one of which is a potential phosphorylation site in
the D1 subdomain, also abolished the NFkappaB activation. Overexpression of
the TRAF domain of TRAF2 or 5 had a dominant negative effect on the
NFkappaB activation mediated by the D1 subdomain, thereby suggesting
involvement of TRAF proteins in the signaling. Thus, the C- terminal 100
amino acid region of CD30 is composed of three independent functional
subdomains, two of which contain binding sites for TRAF proteins. A novel
domain in the cytoplasmic tail mediates NFkappaB activation, without direct
interaction of TRAF2 or 5. Our observations suggest involvement of an
unknown TRAF protein(s) in the signal transduction pathway of CD30.
ARTICLES
A novel domain in the CD30 cytoplasmic tail mediates NFkappaB activation
First Department of Internal Medicine, Faculty of Medicine, University of Tokyo, Japan.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  K. Matsumoto, M. Terakawa, K. Miura, S. Fukuda, T. Nakajima, and H. Saito Extremely Rapid and Intense Induction of Apoptosis in Human Eosinophils by Anti-CD30 Antibody Treatment In Vitro J. Immunol., February 15, 2004; 172(4): 2186 - 2193. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Watanabe, Y. Ogawa, K. Ito, M. Higashihara, M. E. Kadin, L. J. Abraham, T. Watanabe, and R. Horie AP-1 Mediated Relief of Repressive Activity of the CD30 Promoter Microsatellite in Hodgkin and Reed-Sternberg Cells Am. J. Pathol., August 1, 2003; 163(2): 633 - 641. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Horie, T. Watanabe, K. Ito, Y. Morisita, M. Watanabe, T. Ishida, M. Higashihara, M. Kadin, and T. Watanabe Cytoplasmic Aggregation of TRAF2 and TRAF5 Proteins in the Hodgkin-Reed-Sternberg Cells Am. J. Pathol., May 1, 2002; 160(5): 1647 - 1654. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. L. Cotter, J. Zheng, M. Che, D. Niemann, Y. Liu, J. He, E. Thomas, and H. E. Gendelman Regulation of Human Immunodeficiency Virus Type 1 Infection, {beta}-Chemokine Production, and CCR5 Expression in CD40L-Stimulated Macrophages: Immune Control of Viral Entry J. Virol., May 1, 2001; 75(9): 4308 - 4320. [Abstract] [Full Text]
|
|
|
|
|
|
H. Muta, L. H. Boise, L. Fang, and E. R. Podack CD30 Signals Integrate Expression of Cytotoxic Effector Molecules, Lymphocyte Trafficking Signals, and Signals for Proliferation and Apoptosis J. Immunol., November 1, 2000; 165(9): 5105 - 5111. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Horie, V. Gattei, K. Ito, S. Imajo-Ohmi, T. Tange, J. Miyauchi, A. Pinto, M. Degan, A. De Iuliis, F. Tassan Mazzocco, et al. Frequent Expression of the Variant CD30 in Human Malignant Myeloid and Lymphoid Neoplasms Am. J. Pathol., December 1, 1999; 155(6): 2029 - 2041. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Zheng, A. Ghorpade, D. Niemann, R. L. Cotter, M. R. Thylin, L. Epstein, J. M. Swartz, R. B. Shepard, X. Liu, A. Nukuna, et al. Lymphotropic Virions Affect Chemokine Receptor-Mediated Neural Signaling and Apoptosis: Implications for Human Immunodeficiency Virus Type 1-Associated Dementia J. Virol., October 1, 1999; 73(10): 8256 - 8267. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. R. Wong, R. Josien, S. Y. Lee, M. Vologodskaia, R. M. Steinman, and Y. Choi The TRAF Family of Signal Transducers Mediates NF-kappa B Activation by the TRANCE Receptor J. Biol. Chem., October 23, 1998; 273(43): 28355 - 28359. [Abstract] [Full Text] [PDF]
|
|