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A role for the deubiquitinating enzyme USP28 in control of the DNA-damage response

Dong Zhang1, Kathrin Zaugg, Tak W Mak

  • 1Howard Hughes Medical Institute, Department of Genetics, Harvard Partners Center for Genetics and Genomics, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA 02115, USA.

Cell
|August 12, 2006
PubMed

Insights

A newly discovered ubiquitin protease, USP28, stabilizes key proteins in the DNA damage response pathway. This protease is essential for DNA-damage-induced apoptosis, highlighting the role of ubiquitination in DNA repair.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Biochemistry

Background:

  • The Chk2-p53-PUMA pathway is critical for apoptosis following DNA double-strand breaks.
  • Understanding regulators of this pathway is key to comprehending DNA damage responses.

Purpose of the Study:

  • To identify novel regulators of the DNA-damage-induced apoptosis pathway.
  • To elucidate the role of USP28 in DNA damage response and apoptosis.

Main Methods:

  • Analysis of 53BP1 complexes to identify interacting proteins.
  • Utilizing a human cell line to study the Chk2-p53-PUMA pathway.
  • Investigating the stabilization of Chk2 and 53BP1 in response to DNA damage.

Main Results:

  • Discovery of USP28, a ubiquitin protease that regulates the Chk2-p53-PUMA pathway.
  • USP28 is required for the stabilization of Chk2 and 53BP1 after DNA damage.
  • USP28 and Chk2 are essential for DNA-damage-induced apoptosis, partly via p53-mediated PUMA induction.

Conclusions:

  • USP28 plays a vital role in stabilizing key proteins within the DNA damage response.
  • Ubiquitination and deubiquitination are significant regulatory mechanisms in the DNA damage response pathway.
  • USP28 impacts mediators like Mdc1, Claspin, and TopBP1, underscoring its broad role.

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