J Biol Chem. 1997 May 2;272(18):12069-75.

MADD, a novel death domain protein that interacts with the type 1 tumor necrosis factor receptor and activates mitogen-activated protein kinase.External

Schievella, A. R., Chen, J. H., Graham, J. R., Lin, L. L.,
--- - Small Molecule Drug Discovery Group, Genetics Institute, Inc., Cambridge, Massachusetts 02140, USA.
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.
PMID: 9115275External
Arrow2 In vitro interaction Arrow2 In vivo interaction Arrow2 Characterization Arrow2 Functional role Arrow2 top
In vitro interaction
  DD1 DD2 Reference
Family DD1 DD2 Method Species Region Expression Species Region Expression
DD MADD Link MADD Yeast two-hybrid Not specified 1281-1356 Yeast Not specified 1281-1356 Yeast 9115275
DD MADD Link TNFR1 GST fusion protein pull-down Not specified 982-1588 Not specified Not specified 326-413 Not specified 9115275
DD MADD Link TNFR1 Yeast two-hybrid Not specified 982-1588 Yeast Not specified 326-413 Yeast 9115275
DD MADD Link TNFR1 Yeast two-hybrid Not specified 1281-1356 Yeast Not specified 326-413 Yeast 9115275
DD MADD Link TRADD Yeast two-hybrid Not specified 1281-1356 Yeast Not specified 222-289 Yeast 9115275
(Link: click this icon to show interactions only between the two corresponding DDs)
Arrow2 In vitro interaction Arrow2 In vivo interaction Arrow2 Characterization Arrow2 Functional role Arrow2 top
In vivo interaction
  Endogenous
expression
Overexpression DD1 DD2 Reference
Family DD1 DD2 Method Species Region Species Region
DD MADD Link TNFR1 Co-immunoprecipitation COS-7 Not specified Full length Not used 9115275
(Link: click this icon to show interactions only between the two corresponding DDs)