The TAB1-p38α complex aggravates myocardial injury and can be targeted by small molecules

ABSTRACT: There is considerable evidence that inhibition of p38α mitogen-activated protein kinase diminishes cardiac damage during myocardial ischemia. During myocardial ischemia p38α interacts with TAB1, a scaffold protein, which promotes p38α autoactivation; active p38α (pp38α) then trans-phosphorylates TAB1. Previously, we solved the X-ray structure of the p38α-TAB1(384-412) complex. Here we further characterize the interaction by resolving the structure of the pp38α-TAB1(1-438) complex in the active state. Based on this information we created a global knock-in mouse with substitution of four residues on TAB1 (V390A, Y392A, V408G, M409A) we show are required for docking onto p38α. Whereas ablating p38α or TAB1 results in early embryonal lethality, the TAB1 KI mice are viable, develop normally an

INSTRUMENT(S): Illumina HiSeq 2500

ORGANISM(S): Mus musculus

SUBMITTER: Gian De Nicola 

PROVIDER: E-MTAB-6460 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress