Sequence analysis identifies TTRAP, a protein that associates with CD40 and TNF receptor-associated factors, as a member of a superfamily of divalent cation-dependent phosphodiesterases.
CD40 is a member of the tumor necrosis factor (TNF) receptor family. CD40-mediated signal transduction involves the recruitment of several cytoplasmic proteins and induces expression of a large number of genes. TTRAP, a novel protein that interacts with the cytoplasmic domain of CD40 and with TNF-receptor associated factors (TRAFs), has been cloned and shown to inhibit nuclear factor-kappaB activation (NF-kappaB). By using various bioinformatics-based sequence and structure analyses of proteins involved in signaling by the TNF receptor family, we found that TTRAP is a member of a superfamily of Mg(2+)/Mn(2+)-dependent phosphodiesterases. More precisely, our results suggest that TTRAP is related to the human APE1, a Mg(2+)-dependent endonuclease. This potential novel function of TTRAP raises the intriguing possibility for a role of APE1-like DNA-repair endonucleases in TNF receptor family-mediated signaling and functions.
Rodrigues-Lima
F
F
Faculté de Médecine Pitié-Salpêtrière, CNRS UMR 7000, Paris, 75013, France. rlima@ext.jussieu.fr
Josephs
M
M
Katan
M
M
Cassinat
B
B
D020816:Amino Acid Motifs / Q000235:genetics; D000818:Animals; D019013:CD40 Antigens / Q000378:metabolism*; D019757:Carbon-Oxygen Lyases / Q000235:genetics; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D017124:Conserved Sequence; D004260:DNA Repair; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase; D016208:Databases, Factual; D043223:Deoxyribonuclease IV (Phage T4-Induced); D006801:Humans; D008274:Magnesium / Q000378:metabolism; D008345:Manganese / Q000378:metabolism; D051379:Mice; D005810:Multigene Family / Q000235:genetics*; D010727:Phosphoric Diester Hydrolases / Q000235:genetics* / Q000378:metabolism; D051381:Rats; D016415:Sequence Alignment; D020539:Sequence Analysis, Protein; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction
D019013:CD40 Antigens; D002352:Carrier Proteins; D008345:Manganese; D043223:Deoxyribonuclease IV (Phage T4-Induced); D010727:Phosphoric Diester Hydrolases; D019757:Carbon-Oxygen Lyases; C085108:APEX1 protein, human; C486216:Apex1 protein, mouse; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase; D008274:Magnesium