TI  - Modulation of the transcriptional activity of thyroid hormone receptors by
      the tumor suppressor <prot>p53</prot>.
PG  - 4273-7
AB  - Thyroid hormone nuclear receptors (TRs) are ligand-dependent
      transcriptional factors that regulate growth, differentiation, and
      development. The molecular mechanisms by which TRs mediate these effects
      are unclear. One prevailing hypothesis suggests that TRs may cooperate
      with other transcriptional factors to mediate their biological effects. In
      this study, we tested this hypothesis by examining whether the activity of
      TRs is modulated by the tumor suppressor <prot>p53</prot>. <prot>p53</prot> is a nuclear protein
      that regulates gene expression via sequence-specific DNA binding and/or
      direct protein-protein interaction. We found that the  human <prot>TR subtype
      beta 1 </prot>(<prot>h-TR beta 1</prot>)  physically interacted with  <prot>p53</prot>  via its DNA binding
      domain. As a result of this physical interaction, binding of  <prot>h-TR beta 1</prot> 
      to its hormone response elements either as homodimer or as a heterodimer
      with the  <prot>retinoic X receptor</prot>  was inhibited by <prot>p53</prot> in a
      concentration-dependent manner. In transfected cells, wild-type  <prot>p53</prot> 
      repressed the hormone-dependent transcriptional activation of  <prot>h-TR beta 1</prot> .
      In contrast, mutant <prot>p53</prot> either had no effect or activated the
      transcriptional activity of <prot>h-TR beta 1</prot> depending on the type of hormone
      response elements. These results indicate the gene regulating activity of
       TRs  was modulated by  <prot>p53</prot> , suggesting that the cross talk between these two
      transcriptional factors may play an important role in the biology of
      normal and cancer cells.
AD  - Gene Regulation Section, National Cancer Institute, National Institutes of
