Ca2+/Calmodulin-dependent Protein Kinase IV Stimulates Nuclear Factor-κB Transactivation via Phosphorylation of the p65 Subunit

Jang, Moon Kyoo; Goo, Young Hwa; Sohn, Young Chang; Kim, Yun Sung; Lee, Soo Kyung; Kang, Heonjoong; Cheong, Jae Hun; Lee, Jae Woon

doi:10.1074/jbc.m010211200

Cited by 78 publications

(53 citation statements)

References 32 publications

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“…7B). Because SMRT phosphorylation has been associated with its nuclear export (20,25,26), we next analyzed the subcellular distribution of SMRT in these colorectal tumor samples. As shown in Fig.…”

Section: Resultsmentioning

confidence: 99%

Nuclear IKK activity leads to dysregulated Notch-dependent gene expression in colorectal cancer

Fernández‐Majada

Aguilera

Villanueva

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

124

110

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Nuclear functions for IκB kinase (IKK), including phosphorylation of histone H3 and nuclear corepressors, have been recently described. Here, we show that IKK is activated in colorectal tumors concomitant with the presence of phosphorylated SMRT (silencing mediator of retinoic acid and thyroid hormone receptor) corepressor that is aberrantly localized in the cytoplasm. In these tumors, IKKα associates to the chromatin of specific Notch targets, leading to the release of SMRT. Abrogation of IKK activity by BAY11-7082 or by expressing dominant negative IKKα restores the association of SMRT with Notch target genes, resulting in specific gene repression. Finally, BAY11-7082 significantly reduces tumor size in colorectal cancer xenografts (CRC-Xs) implanted in nude mice.

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Section: Resultsmentioning

confidence: 99%

Nuclear IKK activity leads to dysregulated Notch-dependent gene expression in colorectal cancer

Fernández‐Majada

Aguilera

Villanueva

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

124

110

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“…Specific protein kinases such as PI3K, CaMK-IV, ERK and IKKa have been reported to phosphorylate N-CoR and SMRT in different situations. [11][12][13][14][15] Moreover, phosphorylation of SMRT by IKKa results in increased affinity of the corepressor for the 14-3-3 adaptor proteins, thus inducing its cytoplasmic export. The 14-3-3 family is generally regulating subcellular localization of multiple proteins including cdc25, 16 FKHRL1, 17 HDACs 18 or NFkB.…”

Section: Introductionmentioning

confidence: 99%

Aberrant Cytoplasmic Localization of N-CoR in Colorectal Tumors

Fernández‐Majada

Pujadas²,

Vilardell³

et al. 2007

Cell Cycle

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“…3). At the same time, calmodulin stimulates calmodulin-dependent kinases to activate the NF-kB pathway through phosphorylation of NF-kB (4)(5)(6). The change in phosphorylation status of NFAT and NF-kB causes their nuclear translocation and, hence, their activity as transcription factor for their target genes, which include the T cell growth factor IL-2.…”

mentioning

confidence: 99%

Association of CD147 and Calcium Exporter PMCA4 Uncouples IL-2 Expression from Early TCR Signaling

Supper

Schiller

Paster

et al. 2016

The Journal of Immunology

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The Ig superfamily member CD147 is upregulated following T cell activation and was shown to serve as a negative regulator of T cell proliferation. Thus, Abs targeting CD147 are being tested as new treatment strategies for cancer and autoimmune diseases. How CD147 mediates immunosuppression and whether association with other coreceptor complexes is needed have remained unknown. In the current study, we show that silencing of CD147 in human T cells increases IL-2 production without affecting the TCR proximal signaling components. We mapped the immunosuppressive moieties of CD147 to its transmembrane domain and Ig-like domain II. Using affinity purification combined with mass spectrometry, we determined the domain specificity of CD147 interaction partners and identified the calcium exporter plasma membrane calcium ATPase isoform 4 (PMCA4) as the interaction partner of the immunosuppressive moieties of CD147. CD147 does not control the proper membrane localization of PMCA4, but PMCA4 is essential for the CD147-dependent inhibition of IL-2 expression via a calcium-independent mechanism. In summary, our data show that CD147 interacts via its immunomodulatory domains with PMCA4 to bypass TCR proximal signaling and inhibit IL-2 expression

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Ca2+/Calmodulin-dependent Protein Kinase IV Stimulates Nuclear Factor-κB Transactivation via Phosphorylation of the p65 Subunit

Cited by 78 publications

References 32 publications

Nuclear IKK activity leads to dysregulated Notch-dependent gene expression in colorectal cancer

Nuclear IKK activity leads to dysregulated Notch-dependent gene expression in colorectal cancer

Aberrant Cytoplasmic Localization of N-CoR in Colorectal Tumors

Association of CD147 and Calcium Exporter PMCA4 Uncouples IL-2 Expression from Early TCR Signaling

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