The 8-kDa dynein light chain binds to p53-binding protein 1 and mediates DNA damage-induced p53 nuclear accumulation

Kevin W-H Lo1, Ho-Man Kan, Ling-Nga Chan

  • 1Department of Biochemistry, Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, People's Republic of China.

Insights

The 8-kDa light chain (LC8) of dynein binds to p53-binding protein 1 (53BP1), acting as a crucial link. This interaction is essential for the nuclear translocation of tumor suppressor p53 following DNA damage.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • The tumor suppressor protein p53 translocates to the nucleus upon DNA damage, a process dependent on cytoplasmic dynein.
  • The precise molecular mechanism connecting p53 to the dynein motor complex remains unclear.

Purpose of the Study:

  • To elucidate the molecular link between p53 and the dynein motor complex.
  • To investigate the role of p53-binding protein 1 (53BP1) in this interaction.

Main Methods:

  • Protein binding assays to map the LC8-binding domain on 53BP1.
  • In vivo experiments to disrupt the LC8-53BP1 interaction and observe effects on p53 nuclear accumulation.

Main Results:

  • The 8-kDa light chain (LC8) of dynein binds to 53BP1, specifically to a domain N-terminal to its kinetochore localization region.
  • 53BP1 contains two tandem LC8-binding motifs and directly associates with the dynein complex.
  • Disrupting the LC8-53BP1 interaction in vivo inhibited DNA damage-induced nuclear accumulation of p53.

Conclusions:

  • 53BP1 acts as an adaptor, linking p53 to the dynein complex via LC8.
  • LC8 functions as a versatile molecular adaptor, connecting various cargoes to the dynein motor.

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