Act1, a Negative Regulator in CD40- and BAFF-Mediated B Cell Survival

Qian, Youcun; Qin, Jinzhong; Cui, Grace; Naramura, Mayumi; Snow, E Charles; Ware, Carl F.; Fairchild, Robert L.; Omori, Sidne A.; Rickert, Robert C.; Scott, Martin; Kotzin, Brian L.; Li, Xiaoxia

doi:10.1016/j.immuni.2004.09.001

Cited by 139 publications

(177 citation statements)

References 49 publications

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“…Act1 was originally shown to bind to NEMO (Table 2) and ectopic expression suggests that Act1 activates both IKK and JNK (Leonardi et al, 2000;Li et al, 2000;Mauro et al, 2003). In contrast, gene ablation of Act1 suggests a negative regulation of BAFF and CD40 (Qian et al, 2004). Act1 interacts with TRAF3 and CD40 or BAFFR upon stimulation.…”

Section: Nf-jb Activation By Two Distinct Ijb Kinase Pathwaysmentioning

confidence: 99%

“…Act1 may inhibit CD40 and BAFFR signaling through its interaction with TRAF3 by affecting TRAF3 communication with TRAF2 or by affecting stability of NIK. Interestingly, Act1 and TRAF3 mRNAs are induced by BAFF, CD40L and LPS in B cells, suggesting that both regulators cooperate as a feedback control to dampen signaling for B-cell survival and activation (Qian et al, 2004).…”

Section: Nf-jb Activation By Two Distinct Ijb Kinase Pathwaysmentioning

confidence: 99%

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IκB kinase complexes: gateways to NF-κB activation and transcription

2006

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Section: Nf-jb Activation By Two Distinct Ijb Kinase Pathwaysmentioning

confidence: 99%

Section: Nf-jb Activation By Two Distinct Ijb Kinase Pathwaysmentioning

confidence: 99%

IκB kinase complexes: gateways to NF-κB activation and transcription

2006

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“…The SEFIR motif is found in most IL-17R family members, and also in the adaptor molecule Act1 (CIKS). Act1 was originally identified as an activator of NF-κB and p38-MAPK and negatively regulates signaling through CD40 and BAFF [146][147][148]. The presence of a SEFIR domain in Act1 led two groups to demonstrate that Act1 could co-immunoprecipitate with IL-17RA in a SEFIR-dependent manner.…”

Section: Proximal Mediators Of Il-17 Signalingmentioning

confidence: 99%

Structure–function relationships in the IL-17 receptor: Implications for signal transduction and therapy

Shen¹,

Gaffen²

2008

Cytokine

232

245

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IL-17 is the defining cytokine of a newly-described "Th17" population that plays critical roles in mediating inflammation and autoimmunity. The IL-17/IL-17 receptor superfamily is the most recent class of cytokines and receptors to be described, and until recently very little was known about its function or molecular biology. However, in the last year important new insights into the composition and dynamics of the receptor complex and mechanisms of downstream signal transduction have been made, which will be reviewed here.

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“…Treatment of B cells with BLyS, anti-CD40 mAb, and LPS has been shown to increase expression of Act1 (47). Act1-deficient mice have dramatically increased numbers of B cells in the periphery.…”

Section: Discussionmentioning

confidence: 99%

Expression of the Adaptor Protein Hematopoietic Src Homology 2 is Up-Regulated in Response to Stimuli That Promote Survival and Differentiation of B Cells

Herrin

Justement

2006

The Journal of Immunology

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Analysis of hematopoietic Src homology 2 (HSH2) protein expression in mouse immune cells demonstrated that it is expressed at low levels in resting B cells but not T cells or macrophages. However, HSH2 expression is up-regulated within 6–12 h in response to multiple stimuli that promote activation, differentiation, and survival of splenic B cells. HSH2 expression is increased in response to anti-CD40 mAb, the TLR ligands LPS and CpG DNA, and B lymphocyte stimulator (BLyS), a key regulator of peripheral B cell survival and homeostasis. Stimulation of B cells with anti-CD40 mAb, LPS, CpG DNA, or BLyS has previously been shown to induce activation of NF-κB. In agreement with this finding, up-regulation of HSH2 expression in response to these stimuli is blocked by inhibitors of NF-κB activation and is potentiated by stimulation with PMA, suggesting that HSH2 expression is dependent on NF-κB activation. In contrast to CD40, BAFF receptor, TLR4, and TLR9 mediated signaling, stimulation of splenic B cells via the BCR was not observed to induce expression of HSH2 unless the cells had been stimulated previously through CD40. Finally, HSH2 expression is down-regulated in splenic B cells in response to stimulation with IL-21, which has been shown to induce apoptosis, even in the presence of anti-CD40 mAb, LPS, or CpG DNA. IL-21 stimulation also results in down-regulation of antiapoptotic proteins such as Bcl-xL and up-regulation of proapoptotic proteins like Bim. Therefore, HSH2 expression is coordinately up-regulated with known antiapoptotic molecules and directly correlates with B cell survival.

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Act1, a Negative Regulator in CD40- and BAFF-Mediated B Cell Survival

Cited by 139 publications

References 49 publications

IκB kinase complexes: gateways to NF-κB activation and transcription

IκB kinase complexes: gateways to NF-κB activation and transcription

Structure–function relationships in the IL-17 receptor: Implications for signal transduction and therapy

Expression of the Adaptor Protein Hematopoietic Src Homology 2 is Up-Regulated in Response to Stimuli That Promote Survival and Differentiation of B Cells

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