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Stress sensor Gadd45 genes as therapeutic targets in cancer

Alexandra Cretu1, Xiaojin Sha, Jennifer Tront

  • 1Fels Institute for Cancer Research and Molecular Biology, and Department of Biochemistry, Temple University School of Medicine, Philadelphia, PA, 19140 USA.

Cancer Therapy
|August 5, 2009
PubMed

Insights

Growth arrest and DNA damage 45 (Gadd45) proteins act as stress sensors in cellular responses. Their dysregulation in tumors suggests Gadd45 proteins are potential targets for cancer therapy.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Cancer Research

Background:

  • Gadd45 genes are involved in cellular stress responses, including cell cycle arrest, DNA repair, and apoptosis.
  • Gadd45 proteins function as stress sensors, interacting with proteins like PCNA, p21, and stress kinases (p38, JNK).
  • Dysregulated Gadd45 expression is observed in various solid tumors and hematopoietic malignancies.

Purpose of the Study:

  • To review the role of Gadd45 proteins in cellular stress responses.
  • To explore the association of Gadd45 proteins with tumor cell responses to cancer therapeutics.
  • To identify Gadd45 proteins as potential therapeutic targets in oncology.

Main Methods:

  • Literature review of studies on Gadd45 gene and protein functions.
  • Analysis of the interplay between Gadd45 proteins and cell cycle/stress response pathways.
  • Examination of evidence linking Gadd45 expression to cancer development and treatment response.

Main Results:

  • Gadd45 proteins mediate crucial stress signaling pathways.
  • Interactions with PCNA, p21, cdc2/cyclinB1, p38, and JNK kinases highlight Gadd45's regulatory role.
  • Gadd45 proteins are intrinsically linked to tumor cell responses to cancer therapies.

Conclusions:

  • Gadd45 proteins play a significant role in cellular stress responses and cancer.
  • Their involvement in therapeutic responses suggests Gadd45 proteins as novel targets for cancer intervention.
  • Further research is needed to leverage Gadd45 functions for chemotherapeutic drug design.

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