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(The FASEB Journal. 1998;12:1101-1108.)
© 1998 FASEB

BRE: a modulator of TNF-{alpha} action

Chenghua Gua, Alexander Castellinoa, John Y-h. Chanb and Moses V. Chaoa,1

a Department of Cell Biology & Anatomy, Cornell University Medical College, New York, New York 10021, USA
b Chinese University of Hong Kong, Department of Clinical Oncology, Prince of Wales Hospital, Shatin, Hong Kong, China

A stress-responsive gene highly expressed in brain and reproductive organs (BRE) is down-regulated after UV irradiation, DNA damaging agents, or retinoic acid treatment. The human BRE gene encodes a mRNA of 1.9 kb, which gives rise to a protein of 383 amino acids with a molecular size of 44 kilodaltons. BRE is not homologous to any known gene and its function has not been defined. Here we report that BRE was identified multiple times in a yeast two-hybrid screen of a murine cerebellar cDNA library, using the juxtamembrane domain of the p55 tumor necrosis factor {alpha} (TNF) receptor. The interaction between the p55 receptor and BRE was verified by an in vitro biochemical assay by using recombinant fusion proteins and by co-immunoprecipitation of transfected mammalian cells. In the yeast two-hybrid assay, BRE specifically interacted with p55 TNF receptor but not with other TNF family members such as the Fas receptor, the p75 TNF receptor, and p75 neurotrophin receptor. Overexpression of BRE inhibited TNF-induced NF{kappa}B activation, indicating that the interaction of BRE protein with the cytoplasmic region of p55 TNF receptor may modulate signal transduction by TNF-{alpha}.—Gu, C., Castellino, A., Chan, J. Y-H., Chao, M. V. BRE: a modulator of TNF-{alpha} action. FASEB J. 12, 1101–1108 (1998)


Key Words: brain· reproduction·PCR·maltese binding protein




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