Oncogenic conversion of Ets affects redox regulation in-vivo and in-vitro.
The avian acute leukemia virus E26 encodes a fusion protein between viral Gag and the cellular transcription factors cMyb and cEts1(p68). vEts on its own transforms more mature erythroid cells. We have compared the properties of vEts and cEts1(p68). vEts interacts preferentially with an antibody that recognizes the active conformation of the DNA-binding domain. The DNA-binding activity of vEts is particularly sensitive to incubation conditions for band-shift assays, phosphorylation and modification by sulphydryl-specific reagents. Increased sensitivity is due to loss of a protective function of cEts1 C-terminal sequences. cEts2 has a related C-terminal sequence with a similar role. These results suggest that the vEts DNA-binding domain is more accessible to protein-protein interactions and to regulatory mechanisms. Indeed, vEts DNA binding is preferentially inactivated by oxidizing conditions in-vivo. We suggest that the 'open' conformation of the vEts DNA-binding domain favours interactions with other proteins or DNA and facilitates transformation.
Wasylyk
C
C
CNRS-LEGME/INSERM-U. 184, Institut de Chimie Biologique, Faculté de Médecine, Strasbourg, France.
Wasylyk
B
B
D000595:Amino Acid Sequence; D000818:Animals; D000906:Antibodies / Q000276:immunology; D001483:Base Sequence; D002460:Cell Line; D003001:Cloning, Molecular; D003545:Cysteine / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*; D004926:Escherichia coli; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D010084:Oxidation-Reduction; D010766:Phosphorylation; D011485:Protein Binding; D011518:Proto-Oncogene Proteins / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*; D050783:Proto-Oncogene Proteins c-ets; D015682:Retroviridae Proteins, Oncogenic / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*; D014157:Transcription Factors
D000906:Antibodies; D004268:DNA-Binding Proteins; D011518:Proto-Oncogene Proteins; D050783:Proto-Oncogene Proteins c-ets; D015682:Retroviridae Proteins, Oncogenic; D014157:Transcription Factors; C050379:oncogene proteins v-ets; D004247:DNA; D003545:Cysteine