TI  - Several hydrophobic amino acids in the  <prot>p53</prot>  amino-terminal domain are
      required for transcriptional activation, binding to  <prot>mdm-2</prot>  and the
      adenovirus 5 <prot>E1B</prot> 55-kD protein.
PG  - 1235-46
AB  - The <prot>p53</prot> tumor suppressor gene product is a transcriptional activator that
      may be associated with its ability to suppress tumor cell growth. The
      acidic amino terminus of the  <prot>p53</prot>  protein has been shown to contain this
      trans-activation activity as well as the domains for  <prot>mdm-2</prot>  and adenovirus
      5 <prot>E1B</prot> 55-kD protein binding. An extensive genetic analysis of this
      amino-terminal <prot>p53</prot> domain has been undertaken using site-specific
      mutagenesis. The results demonstrate that the acidic residues in the amino
      terminus of <prot>p53</prot> may contribute to, but are not critical for, this
      trans-activation activity. Rather, the hydrophobic amino acid residues
      Leu-22 and Trp-23 of human  <prot>p53</prot>  are both required for trans-activation
      activity, binding to the adenovirus <prot>E1B</prot> 55-kD protein and the human
       <prot>mdm-2</prot> -<prot>p53</prot> protein in vitro. In addition, hydrophobic residues Leu-14 and
      Phe-19 are crucial for the interactions between  <prot>p53</prot>  and  human <prot>mdm-2</prot>
      (<prot>hdm-2</prot>) . Hydrophobic residues Trp-23 and Pro-27 are also important for
      binding to the adenovirus 5 (Ad5) <prot>E1B</prot> 55-kD protein in vitro. These
      mutations have no impact on the ability of the <prot>p53</prot> protein to bind to a
      <prot>p53</prot>-specific DNA element. These results suggest that 2-4 critical
      hydrophobic residues in the amino-terminal domain of the <prot>p53</prot> protein
      interact with the transcriptional machinery of the cell resulting in
      transcriptional activation. These very same hydrophobic residues contact
      the <prot>hdm-2</prot> and Ad5 <prot>E1B</prot> 55-kD oncogene products.
AD  - Department of Molecular Biology, Princeton University, New Jersey
