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Purification of Ubiquitinated p53 Proteins from Mammalian Cells
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The regulatory domain stabilizes the p53 tetramer by intersubunit contacts with the DNA binding domain

Marco Retzlaff1, Julia Rohrberg, Natascha Jennifer Küpper

  • 1Center for Integrated Protein Science Munich at the Department Chemie, Technische Universität München, Lichtenbergstrasse 4, 85747 Garching, Germany.

Journal of Molecular Biology
|October 30, 2012
PubMed

Insights

The tumor suppressor protein p53

Area of Science:

  • Molecular Biology
  • Genetics
  • Biochemistry

Background:

  • The tumor suppressor protein p53, known as the guardian of the genome, has a C-terminal regulatory domain (RD) with debated roles.
  • Previous studies presented conflicting findings on whether the p53 RD acts as a negative or positive regulator of p53 activity, with the underlying mechanisms remaining unclear.

Purpose of the Study:

  • To elucidate the function of the p53 regulatory domain (RD).
  • To investigate the role of a key phosphorylation site within the RD in modulating p53 activity.

Main Methods:

  • Analysis of p53 variants in vivo and in vitro.
  • Biochemical and biophysical techniques to study protein interactions and activity.

Main Results:

  • The p53 RD surprisingly interacts with the DNA binding domain of an adjacent subunit within the p53 tetramer.
  • These intersubunit contacts stabilize the tetrameric structure of p53.
  • This stabilization enhances the transcriptional activity of p53 in a cooperative manner.

Conclusions:

  • The C-terminal regulatory domain (RD) of p53 plays a crucial role in stabilizing its tetrameric structure through intersubunit interactions.
  • Phosphorylation of a specific serine residue within the RD further modulates p53's transcriptional activity.
  • This finding clarifies the enigmatic role of the p53 RD, revealing it as a positive regulator that enhances transcriptional function through structural stabilization.

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