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Two- and Three-Dimensional Live Cell Imaging of DNA Damage Response Proteins
10:24

Two- and Three-Dimensional Live Cell Imaging of DNA Damage Response Proteins

Published on: September 28, 2012

Attenuation of DNA damage checkpoint by PBK, a novel mitotic kinase, involves protein-protein interaction with tumor

Asit K Nandi1, Tamara Ford, Daniel Fleksher

  • 1Greenebaum Cancer Center, University of Maryland School of Medicine, Baltimore, MD 21201, USA. anandi@som.umaryland.edu

Biochemical and Biophysical Research Communications
|May 8, 2007
PubMed

Insights

PDZ-binding kinase (PBK) promotes cancer cell growth by enabling evasion of DNA damage checkpoints. PBK interacts with p53, leading to its downregulation and aberrant cell division, suggesting PBK as a therapeutic target.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Biology

Background:

  • Cancer cells evade surveillance mechanisms, necessitating therapeutic targets.
  • PDZ-binding kinase (PBK) is upregulated in various cancers and is a focus for understanding malignant progression.

Purpose of the Study:

  • To investigate the role of PBK in malignant conversion.
  • To evaluate PBK as a potential therapeutic target in diverse cancers.

Main Methods:

  • Ectopic expression of a phosphomimetic PBK mutant in HT1080 fibrosarcoma cells.
  • Assessment of doxorubicin-induced DNA damage checkpoint adaptation, polyploid cell accumulation, and mitotic phase entry using MPM-2 marker.
  • Analysis of p53 downregulation via biochemical assays and yeast two-hybrid analysis.

Main Results:

  • Ectopic PBK expression in fibrosarcoma cells conferred adaptation to doxorubicin-induced DNA damage.
  • Cells exhibited polyploidization and aberrant entry into mitosis, indicated by MPM-2.
  • PBK directly interacted with p53, leading to p53 downregulation.

Conclusions:

  • PBK plays a role in augmenting tumor cell growth by interfering with DNA damage response pathways.
  • PBK's interaction with p53 provides a mechanism for its oncogenic activity.
  • PBK represents a promising therapeutic target for various cancers.

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