BS69, a Specific Adaptor in the Latent Membrane Protein 1-Mediated c-Jun N-Terminal Kinase Pathway

Wan, Jun; Zhang, Wei; Wu, Liming; Bai, Ting; Zhang, Mingjie; Lo, Kwok Wai; Chui, Yiu‐Loon; Cui, Yan; Tao, Qian; Yamamoto, Masahiro; Akira, Shizuo; Wu, Zhenguo

doi:10.1128/mcb.26.2.448-456.2006

Cited by 46 publications

(58 citation statements)

References 56 publications

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“…BS69/ZMYND11 functions as an adaptor protein bridging LMP1 and TRAF6, a central upstream component in the activation of JNK and other pathways in response to interleukin 1 and bacterial lipopolysaccharide. Activation of TRAF6 by BS69/ZMYND11 appears to be independent of other TRAF6 interacting partners such as TRIF, IRAK1 and IRAK4 thus identifying a novel signalling pathway in EBV-infected cells (Wan et al, 2006). The MYND domain of BS69/ ZMYND11 is essential for direct interaction with LMP1.…”

Section: Rassf1mentioning

confidence: 96%

“…Finally, the MYND-containing protein suppressin has been shown to inhibit cell-cycle entry (LeBoeuf et al, 1998). In addition to its role as a transcriptional corepressor, BS69/ZMYND11 is also essential in latent membrane protein 1 (LMP1)-mediated activation of the JNK pathway (Wan et al, 2006). LMP1 is one of nine latent viral antigens expressed in Epstein-Barr virus (EBV)-infected cells.…”

Section: Rassf1mentioning

confidence: 99%

“…The MYND domain of BS69/ ZMYND11 is essential for direct interaction with LMP1. Although BLU/ZMYND10, which shares 38% amino-acid identity with BS69/ZMYND11 across the MYND domain, does not appear to interact with LMP1 (Wan et al, 2006) it is tempting to speculate that BLU/ ZMYND10 may participate in a similar way in an as yet unidentified signalling pathway. As a MYND-containing protein BLU/ZMYND10 is most likely to be involved in important transcriptional regulation pathways.…”

Section: Rassf1mentioning

confidence: 99%

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Evaluation of the 3p21.3 tumour-suppressor gene cluster

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Section: Rassf1mentioning

confidence: 96%

Section: Rassf1mentioning

confidence: 99%

Section: Rassf1mentioning

confidence: 99%

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Evaluation of the 3p21.3 tumour-suppressor gene cluster

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“…In adenocarcinoma overexpression models, TRAF6 has been hypothesized to interact with LMP1 indirectly through TRADD and/or RIP binding to CTAR2 (reviewed in [20]. More recently BS69 has been described as a potential bridging molecule between LMP1 CTAR2 and TRAF6 [28]. In mouse B cell lines, TRADD does not detectably interact with CTAR2 [21].…”

Section: Lmp1mentioning

confidence: 99%

Roles of TRAF molecules in B lymphocyte function

Xie

Kraus

Stunz

et al. 2008

Cytokine & Growth Factor Reviews

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Tumor necrosis factor receptor associated factors (TRAFs) play a variety of interesting and important roles in the regulation of B lymphocyte function. They act both as cytoplasmic regulatory molecules, and as signal transducers for receptors involved in both innate and adaptive humoral immune responses. In this brief review, we highlight the current state of knowledge of the diverse roles of TRAF molecules in the functions of B lymphocytes. CD40CD40 is the most well-studied member of the TNFR superfamily expressed by B lymphocytes, so its interactions with TRAF molecules have also been intensively investigated. B cell CD40 is important in the induction of B cell survival and expansion, immunoglobulin (Ig) production and isotype switching, upregulation of surface molecules involved in B cell antigen presentation, differentiation to B memory cells, and the production of various cytokines (reviewed in [1]. The TRAF molecules have been shown to contribute to each of these functions (reviewed in [2].In 1994, TRAF3 became the first cytoplasmic molecule demonstrated to associate with CD40 (reviewed in [2]). However, for many years, its roles in CD40 signaling were largely unknown, and are still not completely understood. TRAF3 -/-mice die shortly after birth, but adoptive transfer of fetal liver cells from these mice suggested that their B cells were capable of reconstituting the humoral response [3], implying that TRAF3 is not required to promote CD40-mediated antibody responses. This conclusion was supported by experiments in B cell lines demonstrating that inducible overexpression of TRAF3 inhibits both CD40 responses [4], and cooperation between CD40 and the BCR [5]. Subsequently, B cell lines made completely TRAF3-deficient via gene targeting by homologous recombination show no defects in CD40 signaling overall, and display enhanced CD40-mediated c-jun kinase (JNK) activation and IgM production [6]. Recently, mice made conditionally deficient in TRAF3 only in CD19+ B cells show no deficiencies in CD40 signaling in vitro and have enhanced antibody responses [7]. TRAF2 was initially demonstrated to bind CD40 by exogenous overexpression studies in adenocarcinoma cell lines, in which it promotes JNK activation and the activity of NF-κB reporter genes (reviewed in [2]. Because TRAF2 -/-mice have an early lethal phenotype [8],Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers

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“…Our preliminary data suggest that protein modification, particularly one other than ubiquitination, participates in the degradation of BS69 (data not shown). This is consistent with the finding that high doses of TICAM-1 induce the activation of TRAF E3 ligases [11] and protein modification [12], though the mechanisms have yet to be determined.The previous reports have demonstrated that BS69 physically binds EBV-derived LMP1 and negatively regulates the canonical NF-kB activation by LMP1 [10,13]. Although the regulatory mode of LMP1 is reciprocal to that of TICAM-1, the extranuclear displacement of BS69 commonly occurs in polyI:C-and LMP1-activating pathways.…”

mentioning

confidence: 99%

Oligomerized TICAM‐1 (TRIF) in the cytoplasm recruits nuclear BS69 to enhance NF‐κB activation and type I IFN induction

et al. 2009

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Although adenovirus 5 E1A-binding protein (BS69) is a nuclear protein acting as a transcriptional repressor, we found by an yeast two-hybrid and human cell immunoprecipitation another cytoplasmic function for this protein. BS69 bound Toll-interleukin 1 receptor domain (TIR)-containing adaptor molecule-1 (TICAM-1) (also named TRIF), an adaptor protein that couples with TLR3 around the endosome. BS69 translocated from the nucleus to the cytoplasm when cells were stimulated with dsRNA or transfected with TICAM-1. Confocal analysis of cells with over-expressed TICAM-1 or those stimulated with dsRNA revealed the characteristic ''TICAM-1 speckle'', which reflects signalosome formation necessary for the activation of NF-jB and IFN-regulatory factor (IRF)-3. BS69 was involved in the TICAM-1 complex, and the activation of NF-jB/IRF-3 followed by cytokine production was augmented in the presence of BS69 overexpression. Knockdown of endogenous BS69 resulted in a decrease of IFN-b induction, suggesting that BS69 is a positive regulator for the TLR3-TICAM-1 pathway. These results, together with a recent report showing the negative regulatory properties of BS69 in NF-jB activation by EBVderived latent membrane protein 1, suggest that BS69 harbors dual modes of cytoplasmic NF-jB regulation, positively in the TICAM-1 pathway and negatively in the latent membrane protein 1 pathway.Key words: BS69 . IFN-b . NF-jB . TICAM-1/TRIF . TLR3 Supporting Information available online IntroductionToll-interleukin 1 receptor domain (TIR)-containing adaptor molecule-1 (TICAM-1) acts as an adaptor for TLR3 and activates both the IFN-regulatory factor (IRF)-3 and the IFN-b promoter [1]. TLR3 is localized to the endosome in immature myeloid dendritic cells (mDC) and resting macrophages [2]. Recent imaging analyses revealed that TICAM-1 merges with endosomal TLR3 within 20 min in response to dsRNA stimuli, and after 60 min translocates to form speckles in the cytoplasm which represent the TICAM-1 signalosome [3]. NAP1 and RIP1 are recruited to the TICAM-1 complex, both of which are known to be important factors for activating downstream elements of the TICAM-1 pathway [3,4]. The forced expression of TICAM-1 leads to the formation of multimers in the signalosome complex [4]. To elucidate what molecules constitute the TICAM-1 complex, we screened TICAM-1-binding proteins by Ã These authors contributed equally to this work. [6,7]. The C-terminal MYND domain of BS69 was shown to bind to the PxLxP motif existing on E1A, EBVencoded EBNA2 and a Myc-related cellular protein MGA [8]. Although BS69 is unequivocally a nuclear protein, it has been shown that BS69 interacts with EBV-encoded latent membrane protein 1 (LMP1) in the cytoplasm through its MYND domain and acts as a scaffold protein in the LMP1-mediated JNK pathway by interacting with TRAF6 [9]. Furthermore, a recent report speculated that nuclear BS69 colocalizes with LMP1 in the cytoplasm proximal to the nucleus [10]. The stimulus which induces BS69 protein trafficking, however, remains undeterm...

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BS69, a Specific Adaptor in the Latent Membrane Protein 1-Mediated c-Jun N-Terminal Kinase Pathway

Cited by 46 publications

References 56 publications

Evaluation of the 3p21.3 tumour-suppressor gene cluster

Evaluation of the 3p21.3 tumour-suppressor gene cluster

Roles of TRAF molecules in B lymphocyte function

Oligomerized TICAM‐1 (TRIF) in the cytoplasm recruits nuclear BS69 to enhance NF‐κB activation and type I IFN induction

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