Publications
71 results found
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
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- 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
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- Citations: 231
Bubici C, Papa S, Pham CG, et al., 2004, NF-κB and JNK: an intricate affair., Cell Cycle, Vol: 359, Pages: 1524-1529
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.
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
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- Citations: 73
Zazzeroni F, Papa S, De Smaele E, et al., 2003, Cell signalling (communication arising) - Cell survival and a Gadd45-factor deficiency - Reply, NATURE, Vol: 424, Pages: 742-742, ISSN: 0028-0836
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- Citations: 8
Franzoso G, De Smaele E, Zazzeroni F, et al., 2003, Methods and compositions for modulating apoptosis, WO/2003/028659
Franzoso G, Zazzeroni F, Papa S, 2003, JNK: a killer on a transcriptional leash., Cell Death Differ., Vol: 10, Pages: 13-15
Jin RG, De Smaele E, Zazzeroni F, et al., 2002, Regulation of the <i>gadd45</i>β promoter by NF-κB, DNA AND CELL BIOLOGY, Vol: 21, Pages: 491-503, ISSN: 1044-5498
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- Citations: 61
De Smaele E, Zazzeroni F, Papa S, et al., 2002, Induction of gadd45β by NF-κB down-regulates pro-apoptotic JNK signaling, Publisher: FEDERATION AMER SOC EXP BIOL, Pages: A139-A139, ISSN: 0892-6638
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- Citations: 1
De Smaele E, Zazzeroni F, Papa S, et al., 2001, Induction of <i>gadd45β</i> by NF-κB downregulates pro-apoptotic JNK signalling, NATURE, Vol: 414, Pages: 308-313, ISSN: 0028-0836
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- Citations: 627
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