TRAF2 Is Essential for JNK but Not NF-κB Activation and Regulates Lymphocyte Proliferation and Survival

Lee, Soo Young; Reichlin, Amy; Santana, Angêla Patrícia; Sokol, Karen; Nussenzweig, Michel C.; Choi, Yongwon

doi:10.1016/s1074-7613(00)80390-8

Cited by 437 publications

(423 citation statements)

References 68 publications

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“…Given the poor growth rate and complicated growth conditions (which often causes stress, an unwarranted situation for studying stress response) of early-stage melanoma cultures, further analysis should preferentially rely on freshly dissected tumor samples. The intriguing ability of TRAF2/GCK to elicit either protection or promotion of UVC-induced apoptosis may be in line with TRAF2-dependent or -independent regulation of NF-kB, as implicated from ®ndings in TRAF2 null cells (Yeh et al, 1997), as in lymphocytes expressing the dominant negative form of TRAF2 (Lee et al, 1997). The latter is supported by the observation that forced expression of GCK, but not TRAF2, was su cient to induce NF-kB activities in WM1552 cells, whereas combined expression of TRAF2 and GCK further increased NF-kB activities.…”

Section: Discussionmentioning

confidence: 83%

Role of TRAF2/GCK in melanoma sensitivity to UV-induced apoptosis

2000

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Radiation resistance is a hallmark of human melanoma, and yet mechanisms underlying this resistance are not well understood. We recently established the role of ATF2 in this process, suggesting that stress kinases, which contribute to regulation of ATF2 stability and activity, play an important role in the acquisition of such resistance. Here we demonstrate that changes in the expression and respective activities of TRAF2/GCK occur during melanoma development and regulate its sensitivity to UV-induced apoptosis. Comparing earlyand late-stage melanoma cells revealed low expression of TRAF2 and GCK in early-stage melanoma, which coincided with poor resistance to UV-induced, TNFmediated apoptosis; forced expression of GCK alone or in combination with TRAF2 e ciently increased JNK and NF-kB activities, which coincided with increased protection against apoptosis. Conversely, forced expression of the dominant negative form of TRAF2 or GCK in late-stage melanoma cells reduced NF-kB activity and decreased Fas expression, resulting in a lower degree of UV-induced, Fas-mediated cell death. Our results illustrate a mechanism in which protection from, or promotion of, UV-induced melanoma cell death depends on the nature of the apoptotic cascade (TNF or Fas) and on the availability of TRAF2/GCK, whose expression increases during melanoma progression. Oncogene (2000) 19, 933 ± 942.

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Section: Discussionmentioning

confidence: 83%

Role of TRAF2/GCK in melanoma sensitivity to UV-induced apoptosis

2000

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“…Moreover, TRAF27/7 cells which are defective in TNF-induced JNK activity have been reported to be more susceptible to TNF-induced apoptosis than wild-type cells (Yeh et al, 1997), indicating that TRAF2-mediated JNK activity is antiapoptoic. On the other hand, DN-TRAF2 transgenic mice developed splenomegaly and lymphadenopathy, suggesting that TRAF2 may also possess proapoptotic activity (Lee et al, 1997). In fact, overexpression of TRAF2 is cytotoxic in certain cell types including Hela cells (our unpublished data).…”

Section: Jnk Pathways In Cytokine-induced Apoptosismentioning

confidence: 75%

From receptors to stress-activated MAP kinases

1999

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The cell signaling pathways that culminate in activation of a family of stress-activated MAP kinases are beginning to be de®ned. Determination of cell life and cell death is known to largely depend on the balance of intrinsic life and death signals within cells. Recently, two representative mammalian stress-activated kinases, the JNK and p38 MAP kinases, have been implicated in determination of cell fate by modifying the life, death and di erentiation signals. However, the molecular mechanisms by which extracellular signals are transmitted from membrane receptors to the most upstream kinases in the JNK and p38 signaling modules are not fully understood. This review will provide an overview of current knowledge of molecular links between in¯amma-tory cyokine receptors and stress-activated MAP kinase cascades.

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“…No differences in JNK activation were observed when wild-type and RIP1 À/À cells were treated with TNFa, 8 restricting this function to TRAF2. 11 In contrast, RIP1 is essential for TNFa signalling to p38 MAPK. 12 Following receptor endocytosis, TNF-R1, TRADD, TRAF2 and RIP1 undergo extensive post-translational modifications.…”

Section: Role Of Rip1 In Death Receptor Signallingmentioning

confidence: 99%

RIP1, a kinase on the crossroads of a cell's decision to live or die

et al. 2007

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Binding of inflammatory cytokines to their receptors, stimulation of pathogen recognition receptors by pathogen-associated molecular patterns, and DNA damage induce specific signalling events. A cell that is exposed to these signals can respond by activation of NF-jB, mitogen-activated protein kinases and interferon regulatory factors, resulting in the upregulation of antiapoptotic proteins and of several cytokines. The consequent survival may or may not be accompanied by an inflammatory response. Alternatively, a cell can also activate death-signalling pathways, resulting in apoptosis or alternative cell death such as necrosis or autophagic cell death. Interplay between survival and death-promoting complexes continues as they compete with each other until one eventually dominates and determines the cell's fate. RIP1 is a crucial adaptor kinase on the crossroad of these stress-induced signalling pathways and a cell's decision to live or die. Following different upstream signals, particular RIP1-containing complexes are formed; these initiate only a limited number of cellular responses. In this review, we describe how RIP1 acts as a key integrator of signalling pathways initiated by stimulation of death receptors, bacterial or viral infection, genotoxic stress and T-cell homeostasis. Cell Death and Differentiation (2007) 14, 400-410. doi:10.1038/sj.cdd.4402085Receptor interacting protein (RIP) kinases constitute a family of seven members, all of which contain a kinase domain (KD) (Figure 1a). They are crucial regulators of cell survival and death 1 (Figure 2). Based on sequence similarities, mode of regulation and substrate specificities of their catalytic domain, RIP kinases are classified as serine/threonine kinases and are closely related to members of the interleukin-1-receptorassociated kinase (IRAK) family. RIP1 and RIP2 (CARDIAK/ RICK) also bear a C-terminal domain belonging to the death domain (DD) superfamily, namely, a DD and a caspase recruitment domain (CARD), respectively, allowing recruitment to large protein complexes initiating different signalling pathways. The unique C-terminus of RIP3 bears a RIP homotypic interaction motif (RHIM), which is also present in the intermediate domain (ID) of RIP1. This RHIM domain is sufficient for interaction of RIP1 with RIP3. 1 RIP4 (DIK/PKK) and RIP5 (SgK288) are characterized by the presence of ankyrin repeats in their C-terminal domains. 1 RIP6 (LRRK1) and RIP7 (LRRK2) are RIP members containing a leucine-rich repeat (LRR) motif 1 that may be involved in recognition of pathogen-, damage-or stress-associated molecular patterns (PAMP, DAMP, SAMP). In addition, they harbor Roc/COR domains (Ras of complex proteins/C-terminal of Roc). Binding of GTP to the GTPase-like Roc domain leads to the stimulation of LRRK1 kinase activity. 2 Mutation analysis indicated that the COR domain might be important for transmitting the stimulating signal to the KD. 2 The function of RIP6 and RIP7 is yet unknown; however, mutations in the human LRRK2 gene are associated with both fam...

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TRAF2 Is Essential for JNK but Not NF-κB Activation and Regulates Lymphocyte Proliferation and Survival

Cited by 437 publications

References 68 publications

Role of TRAF2/GCK in melanoma sensitivity to UV-induced apoptosis

Role of TRAF2/GCK in melanoma sensitivity to UV-induced apoptosis

From receptors to stress-activated MAP kinases

RIP1, a kinase on the crossroads of a cell's decision to live or die

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