Zinc finger protein 598 inhibits cell survival by promoting UV-induced apoptosis

Qiaohong Yang1, Romi Gupta1

  • 1Department of Pathology, Yale University School of Medicine, New Haven, CT 06510, USA.

Oncotarget
|February 22, 2018
PubMed

Insights

Zinc finger protein 598 (ZNF598) protects cancer cells from UV-induced apoptosis by upregulating apoptotic gene expression. Loss of ZNF598 confers resistance to UV-induced apoptosis, highlighting its role in cancer cell survival.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Cellular Stress Response

Background:

  • Ultraviolet (UV) radiation is a significant inducer of DNA damage and apoptosis.
  • Cancer cells frequently develop mechanisms to evade apoptosis, contributing to tumor progression and treatment resistance.

Purpose of the Study:

  • To identify novel factors that confer resistance to UV-induced apoptosis in cancer cells.
  • To elucidate the role of Zinc finger protein 598 (ZNF598) in regulating UV-induced apoptosis.

Main Methods:

  • Genome-wide short-hairpin RNA (shRNA) screening to identify key regulators of UV-induced apoptosis.
  • Analysis of ZNF598 and ELK1 expression and phosphorylation levels following UV irradiation.
  • Assessment of apoptosis using annexin V staining and apoptotic gene expression analysis.

Main Results:

  • UV irradiation transcriptionally upregulates ZNF598 expression in cancer cells.
  • ZNF598 knockdown inhibits UV-induced apoptosis, while its ectopic expression promotes it.
  • UV-induced ZNF598 upregulation is dependent on ELK1 activation, and ELK1 knockdown also confers resistance to UV-induced apoptosis.

Conclusions:

  • ZNF598 is a critical mediator of UV-induced apoptosis, acting downstream of ELK1.
  • ZNF598 plays a protective role in cancer cells against UV-induced cell death.
  • Targeting ZNF598 may represent a therapeutic strategy to enhance cancer cell sensitivity to UV-based treatments.

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