Stat3α and Stat3β are two Stat3 isoforms with marked quantitative differences in their DNA binding activities. To examine the molecular basis of the differential DNA binding activities, we measured DNA binding strength and dimer stability, two possible mechanisms responsible for these differences. Stat3α and Stat3β showed no difference in DNA binding strength, i.e. they had similar association and dissociation rates for DNA binding. However, competition analyses performed with dissociating reagents including an anti-phosphotyrosine antibody, SH2 domain protein, and a phosphopeptide demonstrated that Stat3β dimers are more stable than Stat3α dimers. We report here that dimer stability of activated forms plays a critical role in determining DNA binding activity of Stat3 isoforms. We found that C-terminal deletions of Stat3α increased both DNA binding activity and dimer stability of Stat3α. Our findings suggest that the acidic C-terminal region of Stat3α does not interfere with the DNA binding of activated Stat3α dimers, but destabilizes the dimeric forms of Stat3α. We propose that dimer stability described in vitro may be the underlying mechanism of in vivo stability of activated Stat3 proteins, regulating dephosphorylation of tyrosine 705.
|Number of pages||6|
|Journal||Journal of Biological Chemistry|
|Publication status||Published - 2000 Oct 13|
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