Specific binding of MAR/SAR DNA-elements by mutant p53.
Inactivation of the tumor suppressor p53 by single missense point mutations characterizes a large number of human tumors. At least some mutant p53 proteins not only have lost the tumor suppressor function, but at the same time reveal a variety of dominant oncogenic properties. The molecular basis of this 'gain of function' is still unknown. In this report we describe a new biochemical activity of mutant p53, the specific high-affinity interaction with MAR/SAR DNA-elements (nuclear matrix/scaffold attachment regions). This DNA-binding activity can be distinguished from the previously reported DNA-binding activities of p53 by its specificity for mutant p53, the high binding affinity, and the domains of the mutant p53 molecule involved in MAR/SAR DNA-binding. The MAR/SAR-binding region of mutant p53 maps to a bipartite domain consisting of the mutated core region and the C-terminal 60 amino acids, carrying the unspecific DNA-binding domain and the oligomerization motif. MAR/SAR elements are considered as important regulatory elements in a variety of nuclear processes. We propose a model according to which the specific interaction of mutant p53 with MAR/SAR elements might interfere with these processes, thereby exerting pleiotropic oncogenic effects.
Müller
B F
BF
Heinrich-Pette-Institut für Experimentelle Virologie und Immunologie, Hamburg, Germany.
Paulsen
D
D
Deppert
W
W
D000818:Animals; D001483:Base Sequence; D015139:Blotting, Southern; D015153:Blotting, Western; D002460:Cell Line; D004247:DNA / Q000378:metabolism*; D017931:DNA Primers; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008969:Molecular Sequence Data; D017354:Point Mutation; D011485:Protein Binding; D011487:Protein Conformation; D016159:Tumor Suppressor Protein p53 / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism
D017931:DNA Primers; D004268:DNA-Binding Proteins; D016159:Tumor Suppressor Protein p53; D004247:DNA