Abstract
CD74 is an integral membrane protein that was thought to function mainly as an MHC class II chaperone. However, CD74 was recently shown to have a role as an accessory-signaling molecule. Our studies demonstrated that CD74 regulates B-cell differentiation by inducing a pathway leading to the activation of transcription mediated by the NF-kappaB p65/RelA homodimer and its coactivator, TAF(II)105. Here, we show that CD74 stimulation with anti-CD74 antibody leads to an induction of a signaling cascade resulting in NF-kappaB activation, entry of the stimulated cells into the S phase, elevation of DNA synthesis, cell division, and augmented expression of BCL-X(L). These studies therefore demonstrate that surface CD74 functions as a survival receptor.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antigens, Differentiation, B-Lymphocyte / genetics
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Antigens, Differentiation, B-Lymphocyte / immunology*
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B-Lymphocytes / cytology
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B-Lymphocytes / immunology*
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Cell Differentiation / genetics
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Cell Differentiation / immunology*
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Cell Survival / genetics
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Cell Survival / immunology
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DNA / genetics
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DNA / immunology
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Histocompatibility Antigens Class II / genetics
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Histocompatibility Antigens Class II / immunology*
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Humans
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Lymphocyte Activation / immunology*
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Mice
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Mice, Knockout
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S Phase / immunology*
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Signal Transduction / genetics
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Signal Transduction / immunology*
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TATA-Binding Protein Associated Factors / genetics
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TATA-Binding Protein Associated Factors / immunology
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Transcription Factor RelA / genetics
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Transcription Factor RelA / immunology
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Transcription Factor TFIID / genetics
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Transcription Factor TFIID / immunology
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Transcription, Genetic / genetics
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Transcription, Genetic / immunology
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Tumor Cells, Cultured
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bcl-X Protein / genetics
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bcl-X Protein / immunology
Substances
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Antigens, Differentiation, B-Lymphocyte
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Bcl2l1 protein, mouse
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Histocompatibility Antigens Class II
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Rela protein, mouse
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TATA-Binding Protein Associated Factors
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Taf4b protein, mouse
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Transcription Factor RelA
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Transcription Factor TFIID
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bcl-X Protein
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invariant chain
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DNA