Defective anchoring of JNK1 in the cytoplasm by MKK7 in Jurkat cells is associated with resistance to Fas-mediated apoptosis

Wang, Jing; Tang, Ruihong; Lv, Ming; Wang, Qingyang; Zhang, Xueying; Guo, Yuanyuan; Chang, Hong Young; Qiao, Chun‐Feng; He, Xiaoqing; Li, Xinying; Li, Yan; Shen, Beifen; Zhang, Jiyan

doi:10.1091/mbc.e10-06-0492

Cited by 17 publications

(12 citation statements)

References 41 publications

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“…Signal-responsive splicing in T cells www.rnajournal.org 1037 Strikingly, the 178 exons are significantly enriched in genes involved in mediating critical T-cell effector functions, such as cell signaling, proliferation and development, and immune cell trafficking. For example, MAP2K7 controls the activity of the cJun transcription factor, which is essential for expression of cytokines and cell viability; EHMT2 has been implicated in controlling apoptosis; and TIR8 regulates Toll-like receptor signaling and the inflammation response (Hoffmann et al 2008;Drexler et al 2010;Huang et al 2010;Wang et al 2011). Therefore, although the precise functional impact of most of the splicing events we have uncovered remains unexplored, alternative splicing is predicted to play a significant role in shaping the ability of T cells to mount a robust and appropriate immune response.…”

Section: Discussionmentioning

confidence: 99%

Alternative splicing networks regulated by signaling in human T cells

Martínez

Pan²,

Cole³

et al. 2012

RNA

104

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The formation and execution of a productive immune response requires the maturation of competent T cells and a robust change in cellular activity upon antigen challenge. Such changes in cellular function depend on regulated alterations to protein expression. Previous research has focused on defining transcriptional changes that regulate protein expression during T-cell maturation and antigen stimulation. Here, we globally analyze another critical process in gene regulation during T-cell stimulation, alternative splicing. Specifically, we use RNA-seq profiling to identify 178 exons in 168 genes that exhibit robust changes in inclusion in response to stimulation of a human T-cell line. Supporting an important role for the global coordination of alternative splicing following T-cell stimulation, these signal-responsive exons are significantly enriched in genes with functional annotations specifically related to immune response. The vast majority of these genes also exhibit differential alternative splicing between naive and activated primary T cells. Comparison of the responsiveness of splicing to various stimuli in the cultured and primary T cells further reveals at least three distinct networks of signal-induced alternative splicing events. Importantly, we find that each regulatory network is specifically associated with distinct sequence features, suggesting that they are controlled by independent regulatory mechanisms. These results thus provide a basis for elucidating mechanisms of signal pathway-specific regulation of alternative splicing during T-cell stimulation.

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Section: Discussionmentioning

confidence: 99%

Alternative splicing networks regulated by signaling in human T cells

Martínez

Pan²,

Cole³

et al. 2012

RNA

104

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“…36 In unstimulated cells, the basal physiological JNK1 function shows exclusive cytosolic localization. 31,37 By contrast, c-Jun is mostly bound to JNK2, which appears to be responsible for c-Jun ubiquitination and degradation. 29,34 In the cellular response to DNA damage, JNK2 is released from c-Jun, thereby giving more access to active JNK1, resulting in increased JNK1-mediated c-Jun phosphorylation, stability and activity.…”

Section: O N O T D I S T R I B U T Ementioning

confidence: 99%

Genotoxic stress-mediated cell cycle activities for the decision of cellular fate

Erol¹

2011

Cell Cycle

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“…JNK has two ubiquitously expressed isoforms, JNK1 and JNK2, and a tissue-specific isoform JNK3. Each isoform has two different splicing forms, p54 and p46 (9). The activation of JNK is mediated by sequential protein phosphorylation through MAPK kinase (MKK)4 and MKK7, which primarily function as two upstream kinases for JNK activation (10).…”

Section: Introductionmentioning

confidence: 99%

Smad4 inhibits cell migration via suppression of JNK activity in human pancreatic carcinoma PANC-1 cells

Zhang¹,

Cao²,

Pei³

et al. 2016

Oncology Letters

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Abstract. Smad4 is a common Smad and is a key downstream regulator of the transforming growth factor-β signaling pathway, in which Smad4 often acts as a potent tumor suppressor and functions in a highly context-dependent manner, particularly in pancreatic cancer. However, little is known regarding whether Smad4 regulates other signaling pathways involved in pancreatic cancer. The present study demonstrated that Smad4 downregulates c-Jun N-terminal kinase (JNK) activity using a Smad4 loss-of-function or gain-of-function analysis. Additionally, stable overexpression of Smad4 clearly affected the migration of human pancreatic epithelioid carcinoma PANC-1 cells, but did not affect cell growth. In addition, the present study revealed that upregulation of mitogen-activated protein kinase phosphatase-1 is required for the reduction of JNK activity by Smad4, leading to a decrease in vascular endothelial growth factor expression and inhibiting cell migration. Overall, the present findings indicate that Smad4 may suppress JNK activation and inhibit the tumor characteristics of pancreatic cancer cells.

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Defective anchoring of JNK1 in the cytoplasm by MKK7 in Jurkat cells is associated with resistance to Fas-mediated apoptosis

Abstract: MKK7 works as a cytoplasmic anchoring protein for JNK1 in various cell lines but exhibits aberrant nuclear entry in Jurkat cells, which leads to resistance to Fas-mediated apoptosis.

Cited by 17 publications

References 41 publications

Alternative splicing networks regulated by signaling in human T cells

Alternative splicing networks regulated by signaling in human T cells

Genotoxic stress-mediated cell cycle activities for the decision of cellular fate

Smad4 inhibits cell migration via suppression of JNK activity in human pancreatic carcinoma PANC-1 cells

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