Molecular and functional interaction of the ATP-binding cassette transporter A1 with Fas-associated death domain protein.
ATP-binding cassette transporter A1 (ABCA1) is a major regulator of cellular cholesterol and phospholipid homeostasis. Its function has not been fully characterized and may depend on the association with additional proteins. To identify ABCA1-interacting proteins a human liver yeast two-hybrid library was screened with the 144 C-terminal amino acids of ABCA1. Fas-associated death domain protein (FADD) was identified to bind to ABCA1, and this interaction was confirmed by pull-down assays and co-immunoprecipitations. Recombinant expression of a dominant negative form of FADD or the C terminus of ABCA1 in the human hepatoma cell line HepG2 markedly reduced the transfer of phospholipids to apoA-I. This indicates that the binding of additional proteins, one of them being full-length FADD, is required for ABCA1 function. The association of FADD with ABCA1 provides an unexpected link between high density lipoprotein metabolism and an adaptor molecule mainly described in death receptor signal transduction.
Buechler
Christa
C
Institute of Clinical Chemistry and Laboratory Medicine, University of Regensburg, Germany.
Bared
Salim Maa
SM
Aslanidis
Charalampos
C
Ritter
Mirko
M
Drobnik
Wolfgang
W
Schmitz
Gerd
G
D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters / Q000737:chemistry / Q000502:physiology*; D048868:Adaptor Proteins, Signal Transducing; D016632:Apolipoprotein A-I / Q000378:metabolism; D017209:Apoptosis; D002352:Carrier Proteins / Q000737:chemistry / Q000502:physiology*; D002478:Cells, Cultured; D053200:Fas-Associated Death Domain Protein; D006801:Humans; D008075:Lipoproteins, HDL / Q000378:metabolism; D010718:Phosphatidylserines / Q000378:metabolism; D010743:Phospholipids / Q000378:metabolism; D015398:Signal Transduction
C577836:ABCA1 protein, human; D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters; D048868:Adaptor Proteins, Signal Transducing; D016632:Apolipoprotein A-I; D002352:Carrier Proteins; C505533:FADD protein, human; D053200:Fas-Associated Death Domain Protein; D008075:Lipoproteins, HDL; D010718:Phosphatidylserines; D010743:Phospholipids