Jun Turnover Is Controlled Through JNK-Dependent Phosphorylation of the E3 Ligase Itch

Gao, Min; Labuda, Tord; Xia, Ying; Gallagher, Ewen; Fang, Deyu; Liu, Yun‐Cai; Karin, Michael

doi:10.1126/science.1099414

Cited by 366 publications

(448 citation statements)

References 24 publications

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“…87 The E3 ligase Itch can not only catalyze ubiquitination and degradation of PLCg and Bcl10, but also causes depletion of the AP-1 family members JunB and c-Jun upon TCR/CD28 engagement. 88 Thus, Itch can interfere at multiple levels with lymphocyte activation, which is in agreement with the profound immunological disorders that are caused through ablation of Itch in mice. 89,90 In this respect, it is interesting to note that Itch activity can be modulated by JNK, which indicates a novel function of JNK as a negative regulator of T cell signalling.…”

Section: Cd28 Sets the Threshold: The Role Of Ubiquitin Ligasessupporting

confidence: 52%

“…89,90 In this respect, it is interesting to note that Itch activity can be modulated by JNK, which indicates a novel function of JNK as a negative regulator of T cell signalling. 88 Not only do CD28-derived signals impinge on the expression and activity of ubiquitin E3 ligases, but also ICOSmediated signalling is repressed by the RING-type ubiquitin ligase Roquin. 91 Sanroque (san/san) mice, which carry a homozygous mutation in the roquin gene, develop an autoimmune phenotype that resembles human systemic erythematosus and display a substantial increase in previously activated memory T cells.…”

Section: Cd28 Sets the Threshold: The Role Of Ubiquitin Ligasesmentioning

confidence: 99%

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Controlling NF-κB activation in T cells by costimulatory receptors

Schmitz

Krappmann

2006

Cell Death Differ

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Full and productive activation of T lymphocytes relies on the simultaneous delivery of T cell receptor (TCR)-and coreceptor-derived signals. In naïve T cells engagement of the TCR alone causes anergy, while TCR triggering of preactivated T cells results in activation-induced cell death. Costimulatory signals are prominently mirrored by the activation of NF-kB, which needs input from the TCR as well as from coreceptors in order to be fully activated and to fulfil its crucial function in the immune response. Coreceptorgenerated signals tightly control the duration and amplitude of the NF-kB response. The activation of IkB kinase (IKK) complex at the contact zone between a T cell and an antigenpresenting cell offers the unique opportunity to study the spatial organization of IKK activation. Recent studies indicate that coreceptor pathways influence the threshold activities of many signalling mediators and thus act on multiple layers of the NF-kB pathway.

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Section: Cd28 Sets the Threshold: The Role Of Ubiquitin Ligasessupporting

confidence: 52%

Section: Cd28 Sets the Threshold: The Role Of Ubiquitin Ligasesmentioning

confidence: 99%

Controlling NF-κB activation in T cells by costimulatory receptors

Schmitz

Krappmann

2006

Cell Death Differ

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“…Recent studies provide insight into the mechanisms of c-Jun and JunB turnover. 13,14 Interestingly, Gao et al 14 demonstrated that JunB (and c-Jun) abundance can be regulated by extracellular stimuli in T-cells through Jun-N terminal kinase (JNK)-dependent phosphorylation of the novel E3 ligase Itch.…”

Section: Discussionmentioning

confidence: 99%

JunB expression is a common feature of CD30+ lymphomas and lymphomatoid papulosis

et al. 2005

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JunB is a member of the Jun family of proteins that are components of the AP-1 transcription factor complex. AP-1 is involved in cell proliferation and apoptosis. Recent evidence suggests that Hodgkin and ReedSternberg cells overexpress JunB and that JunB facilitates constitutive CD30 expression by binding to an AP-1 site in the CD30 promoter. In this study we surveyed JunB expression in a variety of CD30 þ lymphoma types including 42 cases of anaplastic large cell lymphoma, 36 classical Hodgkin lymphoma, 15 cutaneous anaplastic large cell lymphoma, and 11 CD30 þ diffuse large B-cell lymphoma. In addition, seven cases of nodular lymphocyte-predominant Hodgkin lymphoma and 42 diffuse large B-cell lymphoma, known to be CD30À, were analyzed. JunB expression was assessed using tissue microarrays, immunohistochemistry and a monoclonal antibody specific for JunB. Expression of JunB was observed in 41 of 42 cases of anaplastic large cell lymphoma, including all 21 cases positive for anaplastic lymphoma kinase and 20 of 21 (95%) negative for anaplastic lymphoma kinase. JunB was also expressed in all cases of classical Hodgkin lymphoma, cutaneous anaplastic large cell lymphoma and CD30 þ diffuse large B-cell lymphoma, and in lymphomatoid papulosis. By contrast, all nodular lymphocyte-predominant Hodgkin lymphomas and diffuse large B-cell lymphomas that were CD30À were also JunBÀ. We conclude that JunB is expressed in virtually all CD30 þ lymphomas and is a potential target for experimental therapy in patients with these tumors.

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“…One ligase is the human COP1, which forms a multi-subunit ubiquitin ligase complex, DCX hDET1ÀhCOP1 and promotes c-Jun degradation regardless of c-Jun's phosphorylation status (Wertz et al, 2004). A second ligase is Itch, whose E3 ligase activity needs to be activated by JNKs through phosphorylation, causing the degradation of c-Jun in a manner independent of c-Jun phosphorylation by JNKs (Gao et al, 2004). The third c-Jun E3 ligase is Fbw7 (also called Fbxw7, CDC4, AGO and SEL10; Nateri et al, 2004), which forms a ligase complex with SKP1 and CUL1 that is referred to as SCF FBW7 (Welcker and Clurman, 2008).…”

Section: Introductionmentioning

confidence: 99%