Determination of the human c-Abl consensus DNA binding site.
c-Abl tyrosine kinase, an essential protein of the cell cycle signalling pathways, is implicated in the regulation of RNA polymerase II activity, apoptosis and DNA repair. Its DNA binding activity is important for its biological functions. However, the molecular basis of c-Abl interaction with DNA remains largely unclear. We delimited the human c-Abl DNA binding domain and identified its preferred binding site, 5'-A(A/C)AACAA(A/C). The central AAC motif is highly conserved and constitutes the major core element in the binding sites. EMSAs and footprinting experiments were performed to explore how the c-Abl fusion protein recognizes specific sequences in DNA.
David-Cordonnier
M H
MH
INSERM U 124 Onco-hématologie moléculaire, Institut de Recherches sur le Cancer de Lille, France.
Hamdane
M
M
Bailly
C
C
D'Halluin
J C
JC
D000595:Amino Acid Sequence; D001483:Base Sequence; D001665:Binding Sites; D017124:Conserved Sequence; D004247:DNA / Q000378:metabolism*; D018983:DNA Footprinting; D003850:Deoxyribonuclease I / Q000378:metabolism; D004586:Electrophoresis / Q000379:methods; D006801:Humans; D008969:Molecular Sequence Data; D017433:Protein Structure, Secondary; D016315:Proto-Oncogene Proteins c-abl / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D017384:Sequence Deletion; D012984:Software; D013379:Substrate Specificity
D011993:Recombinant Fusion Proteins; D004247:DNA; D016315:Proto-Oncogene Proteins c-abl; D003850:Deoxyribonuclease I