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TGF-beta directly targets cytotoxic T cell functions during tumor evasion of immune surveillance

Tumors escape from immune surveillance by producing the immunosuppressive cytokine TGF-beta. However, the mechanism by which TGF-beta inhibits T cell-mediated tumor clearance in vivo is unknown. We demonstrate that TGF-beta acts on cytotoxic T...

Authors: Thomas DA and Massague J

Interferon regulatory factor 4 negatively regulates the production of proinflammatory cytokines by macrophages in response to LPS

A member of the IFN regulatory factor (IRF) family of transcription factors, IRF-4 is expressed in lymphocytes and macrophage/dendritic cells. Studies using IRF-4-deficient mice have revealed the critical roles of IRF-4 in lymphocyte responses....

Authors: Honma K, Udono H, Kohno T, Yamamoto K, Ogawa A, Takemori T, Kumatori A, Suzuki S, Matsuyama T and...

A novel orally active proteasome inhibitor induces apoptosis in multiple myeloma cells with mechanisms distinct from Bortezomib

Bortezomib therapy has proven successful for the treatment of relapsed and/or refractory multiple myeloma (MM); however, prolonged treatment is associated with toxicity and development of drug resistance. Here, we show that the novel proteasome...

Authors: Chauhan D, Catley L, Li G, Podar K, Hideshima T, Velankar M, Mitsiades C, Mitsiades N, Yasui H,...

Negative regulation of Toll-like-receptor signaling by IRF-4

The recognition of microbial components by Toll-like receptors (TLRs) is an event central to the activation of innate and adaptive immune systems. TLR activation triggers the induction of downstream target genes, wherein the TLR-interacting adaptor...

Authors: Negishi H, Ohba Y, Yanai H, Takaoka A, Honma K, Yui K, Matsuyama T, Taniguchi T and Honda K

Dishevelled (Dvl-2) activates canonical Wnt signalling in the absence of cytoplasmic puncta

Dishevelled family proteins are multidomain intracellular transducers of Wnt signals. Ectopically expressed mammalian Dishevelled 2 (Dvl-2) activates downstream signalling and localises to cytoplasmic puncta. It has been suggested that these...

Authors: Smalley MJ, Signoret N, Robertson D, Tilley A, Hann A, Ewan K, Ding Y, Paterson H and Dale TC

Identification of an ectodomain within the LAR protein tyrosine phosphatase receptor that binds homophilically and activates signalling pathways promoting neurite outgrowth

Elucidation of mechanisms by which receptor protein tyrosine phosphatases (PTPs) regulate neurite outgrowth will require characterization of ligand-receptor interactions and identification of ligand-induced signalling components mediating neurite...

Authors: Yang T, Yin W, Derevyanny VD, Moore LA and Longo FM

The PDZ binding motif of HTLV-1 tax promotes virus mediated T-cell proliferation in vitro and persistence in vivo

HTLV-1 cellular transformation and disease induction is dependent on expression of the viral Tax oncoprotein. PDZ is a modular protein interaction domain used in organizing signaling complexes in eukaryotic cells through recognition of a specific...

Authors: Xie L, Yamamoto B, Haoudi A, Semmes OJ and Green PL

Regulation of the germinal center gene program by interferon (IFN) regulatory factor 8/IFN consensus sequence-binding protein

Interferon (IFN) consensus sequence-binding protein/IFN regulatory factor 8 (IRF8) is a transcription factor that regulates the differentiation and function of macrophages, granulocytes, and dendritic cells through activation or repression of target...

Authors: Lee CH, Melchers M, Wang H, Torrey TA, Slota R, Qi CF, Kim JY, Lugar P, Kong HJ, Farrington L, van...

CD38 Expression Is Insensitive to Steroid Action in Cells Treated with Tumor Necrosis Factor- and Interferon- by a Mechanism Involving the Up-Regulation of the Glucocorticoid Receptor beta Isoform

Evidence shows that the CD38 molecule, recently involved in the two main features of asthma, bronchial hyper-responsiveness and airway inflammation, could represent a new potential therapeutic target for asthma. In this study, we investigated whether...

Authors: Tliba O, Cidlowski J and Amrani Y

The identification and characterization of two phosphatidylinositol-4,5-bisphosphate 4-phosphatases

Numerous inositol polyphosphate 5-phosphatases catalyze the degradation of phosphatidylinositol-4,5-bisphosphate (PtdIns-4,5-P(2)) to phosphatidylinositol-4-phosphate (PtdIns-4-P). An alternative pathway to degrade PtdIns-4,5-P(2) is the hydrolysis...

Authors: Ungewickell A, Hugge C, Kisseleva M, Chang SC, Zou J, Feng Y, Galyov EE, Wilson M and Majerus PW

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