Publications
43 results found
Bubici C, Papa S, Pham CG, et al., 2006, The NF-κB-mediated control of ROS and JNK signaling, Histology and Histopathology, Vol: 21, Pages: 69-80, ISSN: 0213-3911
NF-κB/Rel transcription factors are best known for their roles in innate and adaptive immunity and inflammation. They also play a central role in promoting cell survival. This latter activity of NF-κB antagonizes programmed cell death (PCD) induced by the proinflammatory cytokine tumor necrosis factor (TNF)α and plays an important role in immunity, lymphopoiesis, osteogenesis, tumorigenesis and radio- and chemo-resistance in cancer. With regard to TNFα, the NF-κB-mediated inhibition of PCD seems to involve an attenuation of the c-Jun-N-terminal kinase (JNK) cascade mediated through the induction of select downstream targets such as the caspase inhibitor XIAP, the zinc-finger protein A20, and the inhibitor of the MKK7/JNKK2 kinase, Gadd45β/Myd118. Notably, NF-κB also blunts accumulation of reactive oxygen species (ROS), which themselves are pivotal elements for induction of PCD by TNFα, and this suppression of ROS formation mediates an additional protective activity recently ascribed to NF-κB. The antioxidant activity of NF-κB has been shown to depend upon upregulation of both Ferritin heavy chain (FHC) - a component of Ferritin, the primary iron-storage protein complex found in cells - and of the mitochondrial enzyme Mn++ superoxide dismutase (Mn-SOD). Indeed, the inductions of Mn-SOD and FHC represent another important means through which NF-κB controls proapoptotic JNK signaling triggered by TNFα. These findings might enable the development of new, more targeted approaches to treatment of diseases sustained by a deregulated activity of NF-κB, including some cancers and chronic inflammatory conditions.
Bubici C, Papa S, Pham CG, et al., 2006, The NF-κB-mediated control of ROS and JNK signaling, HISTOLOGY AND HISTOPATHOLOGY, Vol: 21, Pages: 69-80, ISSN: 0213-3911
- Author Web Link
- Cite
- Citations: 151
Yang H, Bocchetta M, Kroczynska B, et al., 2006, TNFα inhibits asbestos induced cytotoxicity via a NF-κB-dependent pathway: a possible mechanism for asbestos induced oncogenesis., Proc. Natl. Acad. Sci. (U.S.A.), Vol: 103, Pages: 10397-10402
Papa S, Bubici C, Pham CG, et al., 2005, NF-κB meets ROS:: an 'ron-ic' encounter, CELL DEATH AND DIFFERENTIATION, Vol: 12, Pages: 1259-1262, ISSN: 1350-9047
- Author Web Link
- Cite
- Citations: 21
Pham CG, Papa S, Bubici C, et al., 2005, Oxygen JNKies: Phosphatases overdose on ROS, DEVELOPMENTAL CELL, Vol: 8, Pages: 452-454, ISSN: 1534-5807
- Author Web Link
- Cite
- Citations: 14
Pham CG, Papa S, Bubici C, et al., 2005, In the crosshairs: NF-κB targets the JNK signaling cascade., Curr. Med. Chem. - AIAA, Vol: 4, Pages: 569-576
Bubici C, Papa S, Pham CG, et al., 2004, NF-κB and JNK -: An intricate affair, CELL CYCLE, Vol: 3, Pages: 1524-1529, ISSN: 1538-4101
- Author Web Link
- Cite
- Citations: 88
Pham CG, Bubici C, Zazzeroni F, et al., 2004, Ferritin heavy chain upregulation by NF-κB inhibits TNFα-induced apoptosis by suppressing reactive oxygen species, CELL, Vol: 119, Pages: 529-542, ISSN: 0092-8674
- Author Web Link
- Cite
- Citations: 516
Papa S, Zazzeroni F, Pham CG, et al., 2004, Linking JNK signaling to NF-κB:: a key to survival, JOURNAL OF CELL SCIENCE, Vol: 117, Pages: 5197-5208, ISSN: 0021-9533
- Author Web Link
- Cite
- Citations: 231
Barnhart BC, Legembre P, Pietras E, et al., 2004, CD95 ligand induces motility and invasiveness of apoptosis-resistant tumor cells, EMBO JOURNAL, Vol: 23, Pages: 3175-3185, ISSN: 0261-4189
- Author Web Link
- Cite
- Citations: 232
Papa S, Zazzeroni F, Bubici C, et al., 2004, Gadd45{beta} mediates the NF-kappaB suppression of JNK signalling by targeting MKK7/JNKK2., Nat. Cell Biol., Vol: 6, Pages: 146-153
NF-kappa B/Rel transcription factors control apoptosis, also known as programmed cell death. This control is crucial for oncogenesis, cancer chemo-resistance and for antagonizing tumour necrosis factor alpha (TNFalpha)-induced killing. With regard to TNFalpha, the anti-apoptotic activity of NF-kappa B involves suppression of the c-Jun N-terminal kinase (JNK) cascade. Using an unbiased screen, we have previously identified Gadd45{beta}/Myd118, a member of the Gadd45 family of inducible factors, as a pivotal mediator of this suppressive activity of NF-kappaB. However, the mechanisms by which Gadd45{beta} inhibits JNK signalling are not understood. Here, we identify MKK7/JNKK2--a specific and essential activator of JNK--as a target of Gadd45 beta, and in fact, of NF-kappa B itself. Gadd45{beta} binds to MKK7 directly and blocks its catalytic activity, thereby providing a molecular link between the NF-kappaB and JNK pathways. Importantly, Gadd45{beta} is required to antagonize TNFalpha-induced cytotoxicity, and peptides disrupting the Gadd45{beta}/MKK7 interaction hinder the ability of Gadd45{beta}, as well as of NF-kappaB, to suppress this cytotoxicity. These findings establish a basis for the NF-kappaB control of JNK activation and identify MKK7 as a potential target for anti-inflammatory and anti-cancer therapy.
Bubici C, Papa S, Pham CG, et al., 2004, NF-κB and JNK: an intricate affair., Cell Cycle, Vol: 359, Pages: 1524-1529
Zazzeroni F, Papa S, Algeciras-Schimnich A, et al., 2003, Gadd45β mediates the protective effects of CD40 costimulation against Fas-induced apoptosis, BLOOD, Vol: 102, Pages: 3270-3279, ISSN: 0006-4971
- Author Web Link
- Cite
- Citations: 73
This data is extracted from the Web of Science and reproduced under a licence from Thomson Reuters. You may not copy or re-distribute this data in whole or in part without the written consent of the Science business of Thomson Reuters.