The C-terminal Sterile α Motif and the Extreme C Terminus Regulate the Transcriptional Activity of the α Isoform of p73*

p73, a member of the p53 family, is expressed from two separate promoters, generating TA and ΔN variants. Each variant potentially encodes at least seven alternatively spliced isoforms (α–η). Interestingly, we and others have shown that the α isoform of p73 has a weaker transcriptional activity than the β isoform. Because the α isoform has an extended C terminus consisting of a sterile α motif (SAM) and an extreme C terminus, it appears that the C terminus is inhibitory. However, how the C terminus inhibits the transcriptional activity of p73 has not been determined. Here, we found that both the SAM and the extreme C terminus exert their inhibitory activity by preventing the accessibility of p300/CBP to the activation domain in p73. Specifically, we showed that the SAM and the extreme C terminus together or individually are capable of repressing the function of p73 activation domain, but neither interacts directly with the activation domain, or suppresses the DNA-binding activity, of the p73 protein. We also showed that the intact state of the SAM and the extreme C terminus is essential for their inhibitory functions such that a small deletion of either the SAM or the extreme C terminus abolishes its inhibitory activity. Furthermore, we showed that both inhibitory domains in the C terminus are capable of suppressing the function of a cis heterologous activation domain from p53 or Gal4. Finally, we showed that both inhibitory domains suppress the ability of p73 to interact with the transcriptional coactivators p300/CBP that are necessary for the initiation of transcription.

• Publication year

  2005

• Venue

  Journal of Biological Chemistry

• Publication date

  2005-05-20

• Fields of study

  Biology

• Identifiers
  DOI 10.1074/JBC.M413889200
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar

• No claims are published for this paper.

• No concepts are published for this paper.

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