Co-activation of ERK, NF-κB, and GADD45β in Response to Ionizing Radiation

Wang, Tieli; Hu, Yongfeng; Dong, Suchuan; Fan, Ming; Tamae, Daniel; Ozeki, Munetaka; Gao, Qian; Gius, David; Li, Jian Jian

doi:10.1074/jbc.m410982200

Cited by 68 publications

(62 citation statements)

References 61 publications

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“…It has been long observed that IRinduced GADD45B expression is linked to p53 pathways. Recently, Wang and colleagues demonstrated that NK-κB, ERK and GADD45ß are co-activated by ionizing radiation (IR) and coordinate in a loop-like signaling network to defend cells against the cytotoxicity induced by ionizing radiation and increase cell survival (24). Data from our study show that GADD45B was elevated in ISK cells after IR exposure.…”

Section: Discussionsupporting

confidence: 51%

Differential expression profiling of gene response to ionizing radiation in two endometrial cancer cell lines with distinct radiosensitivities

Jiang²,

Wen³

et al. 2009

Oncol Rep

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Section: Discussionsupporting

confidence: 51%

Differential expression profiling of gene response to ionizing radiation in two endometrial cancer cell lines with distinct radiosensitivities

Jiang²,

Wen³

et al. 2009

Oncol Rep

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“…It is tempting to speculate, therefore, that the antagonistic effects of telomerase and TGF-b on MAP kinase and protein kinase C signaling may account for the antagonistic effects of telomerase and TGF-b on gene expression. In fact, the expression of the majority (12/19) of genes that are downregulated by mTert (Figure 3a) has been reported to be increased by MAP kinase and/or protein kinase C signaling (Bhlhb2 (Collado et al, 2005), Btg2 (Ryu et al, 2004), Dusp6 (Smith et al, 2005), Eln (Liu et al, 2003), Egr2 (Keeton et al, 2003), Junb/Fosb (Mechta et al, 1997;Hodge et al, 1998;Balasubramanian et al, 2002), Gadd45b (Wang et al, 2005b), Ier3 (Kondratyev et al, 1996), Klf4 (Chen and Tseng, 2005), Nfil3 (Kuribara et al, 1999), and Nr4a1 (Lim et al, 1995). Future work is required to unravel the detailed mechanisms by which telomerase interferes with intracellular signaling pathways and to define the relevance of such interactions on biologically relevant pathways such as TGF-b signaling.…”

Section: Discussionmentioning

confidence: 99%

Expression of mTert in primary murine cells links the growth-promoting effects of telomerase to transforming growth factor-β signaling

et al. 2006

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Here, we show that ectopic expression of the catalytic subunit of mouse telomerase (mTert) confers a growth advantage to primary murine embryonic fibroblasts (MEFs), which have very long telomeres, as well as facilitates their spontaneous immortalization and increases their colony-forming capacity upon activation of oncogenes. We demonstrate that these telomere lengthindependent growth-promoting effects of mTert overexpression require catalytically active mTert, as well as the formation of mTert/Terc complexes. The gene expression profile of mTert-overexpressing MEFs indicates that telomerase enhances growth in these cells through the repression of growth-inhibiting genes of the transforming growth factor-beta (TGF-b) signaling network. We functionally validate this result by showing that mTert abrogates the growth-inhibitory effect of TGF-b in MEFs, thus demonstrating that telomerase increments the proliferative potential of primary mouse embryonic fibroblasts by targeting the TGF-b pathway.

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“…After exposure to a single high dose of IR (5 Gy), ERK is activated along with an enhancement of the NF-κB transactivation in human breast cancer cells [81]. This coactivation of NF-κB and ERK occurs in a pattern of mutual dependence and is involved in activating GADD45β to defend cells against the cytotoxicity induced by IR.…”

Section: Erk Is Strongly Induced By High Doses Of Ir Via Membrane-assmentioning

confidence: 99%

“…There are three mitogen-activated protein kinases (MAPKs), i.e., extracellular signal-regulated kinase (ERK), JNK, and p38, which are all closely related to NF-κB activation [79][80][81]. ERK, which is also able to activate NF-κB, tends to induce antiapoptosis, whereas the JNK and p38 pathways promote apoptosis.…”

Section: Nf-κb Activation By Ir-induced Cytokinesmentioning

confidence: 99%

NF-κB-mediated adaptive resistance to ionizing radiation

Ahmed

2008

Free Radical Biology and Medicine

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198

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Ionizing radiation (IR) began to be a powerful medical modality soon after Wilhelm Röntgen's discovery of X-rays in 1895. Today, more than 50% of cancer patients receive radiotherapy at some time during the course of their disease. Recent technical developments have significantly increased the precision of dose delivery to the target tumor, making radiotherapy more efficient in cancer treatment. However, tumor cells have been shown to acquire a radioresistance that has been linked to increased recurrence and failure in many patients. The exact mechanisms by which tumor cells develop an adaptive resistance to therapeutic fractional irradiation are unknown, although low-dose IR has been well defined for radioadaptive protection of normal cells. This review will address the radioadaptive response, emphasizing recent studies of molecular-level reactions. A prosurvival signaling network initiated by the transcription factor NF-κB, DNA-damage sensor ATM, oncoprotein HER-2, cell cyclin elements (cyclin B1), and mitochondrial functions in radioadaptive resistance is discussed. Further elucidation of the key elements in this prosurvival network may generate novel targets for resensitizing the radioresistant tumor cells. KeywordsIonizing radiation; NF-κB; Signal transduction; Adaptive radiation resistance; Free radicals Does ionizing radiation (IR) induce radioadaptive resistance?Acquired tumor radioresistance can be induced during radiotherapy due to tumor repopulation [1]. Although tumor radioresistance stands as an fundamental barrier limiting the effectiveness of radiation therapy, the exact molecular mechanisms underlying the radioadaptive response are largely unknown. The term radioadaptive response was originally described as a reduced cell sensitivity to a higher challenging dose when a smaller inducing radiation dose had been applied earlier [2]. Olivieri et al. [3] first described an adaptive response of human lymphocytes to ionizing radiation. Since then a substantial number of reports make a strong case for the existence of cellular radioprotective mechanisms that can be activated in response to a small dose of ionizing radiation. It is assumed that a specific prosurvival signaling network is induced in irradiated mammalian cells. Such prosurvival molecular networks, especially induced in the tumor under clinical fractional irradiation, have not yet been fully elucidated. New therapeutic means including manipulating the radioadaptive response require further knowledge of the consequences of the activation of such prosurvival pathways.Exposure to low levels of IR is evidenced to generate beneficial effects for mammalian cells with respect to the maintenance of genomic integrity and the ability to repair damaged DNA [4,5]. Although the IR doses applied vary on a large scale, a similar radioadaptive resistance is significantly induced in many other species, including Escherichia coli, protozoa, algae, *Corresponding author. Fax: +1 765 496 1377. E-mail address: jjli@purdue.edu (J.J. Li). . In addition, h...

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Co-activation of ERK, NF-κB, and GADD45β in Response to Ionizing Radiation

Cited by 68 publications

References 61 publications

Differential expression profiling of gene response to ionizing radiation in two endometrial cancer cell lines with distinct radiosensitivities

Differential expression profiling of gene response to ionizing radiation in two endometrial cancer cell lines with distinct radiosensitivities

Expression of mTert in primary murine cells links the growth-promoting effects of telomerase to transforming growth factor-β signaling

NF-κB-mediated adaptive resistance to ionizing radiation

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