Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0268596 (EMA)
 2,520 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The death domain of the type 1 tumor necrosis factor receptor (TNFR1) mediates interactions with several proteins involved in signaling the downstream effects of TNF. We have used the yeast interaction trap to isolate a protein, MADD, that associates with the death domain of TNFR1 through its own C-terminal death domain. MADD interacts with TNFR1 residues that are critical for signal generation and coimmunoprecipitates with TNFR1, implicating MADD as a component of the TNFR1 signaling complex. Importantly, we have found that overexpression of MADD activates the mitogen-activated protein (MAP) kinase extracellular signal-regulated kinase (ERK), and expression of the MADD death domain stimulates both the ERK and c-JUN N-terminal kinase MAP kinases and induces the phosphorylation of cytosolic phospholipase A2. These data indicate that MADD links TNFR1 with MAP kinase activation and arachidonic acid release and provide further insight into the mechanisms by which TNF exerts its pleiotropic effects.
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PMID:MADD, a novel death domain protein that interacts with the type 1 tumor necrosis factor receptor and activates mitogen-activated protein kinase. 911 75

We have previously isolated and sequenced the cDNA of a novel gene, DENN, that exhibits differential mRNA expression in normal and neoplastic cells. The open reading frame of 4761 nucleotides encodes a putative hydrophilic protein of 1587 amino acids with a calculated molecular mass of 176,431 Da. Within DENN cDNA lies an alternative exon segment of 129 nucleotides encoding 43 amino acids, which may be excluded from some transcripts by alternative splicing. The serine- and leucine-rich DENN protein possesses a RGD cellular adhesion motif and a leucine-zipper-like motif associated with protein dimerization, and shows partial homology to the receptor binding domain of tumor necrosis factor alpha. DENN is virtually identical to MADD, a human MAP kinase-activating death domain protein that interacts with type I tumor necrosis factor receptor. DENN displays significant homology to Rab3 GEP, a rat GDP/GTP exchange protein specific for Rab3 small G proteins implicated in intracellular vesicle trafficking. DENN also exhibits strong similarity to Caenorhabditis elegans AEX-3, which interacts with Rab3 to regulate synaptic vesicle release. Composed of 15 exons (ranging in size from 73 to 1230 bp) and 14 introns (varying from about 170 bp to 5.3 kb), the DENN gene is estimated to span at least 28 kb. The alternative splicing event was traced to an alternative 5' donor site involving exon 7. DENN was mapped to chromosome region 11p11.21-p11.22 by FISH. Using polyclonal antibodies against a synthetic peptide, Western blotting of MOLT-4 T-lymphoblastic leukemic cell proteins and immunoblotting of subcellular fractions of MOLT-4 cells and PLC/PRF/5 liver cancer cells yielded data corroborating the alternative splicing mechanism that generates two variant isoforms of the DENN protein that display differential expression in cells of different lineages.
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PMID:The human DENN gene: genomic organization, alternative splicing, and localization to chromosome 11p11.21-p11.22. 979 3