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THAP1 is a nuclear proapoptotic factor that links prostate-apoptosis-response-4 (Par-4) to PML nuclear bodies.

Promyelocytic leukemia (PML) nuclear bodies (PML NBs) are discrete subnuclear domains organized by the promyelocytic leukemia protein PML, a tumor suppressor essential for multiple apoptotic pathways. We have recently described a novel family of cellular factors, the THAP proteins, characterized by the presence at their amino-terminus of an evolutionary conserved putative DNA-binding motif, designated THAP domain. Here, we report that THAP1 is a novel nuclear proapoptotic factor associated with PML NBs, which potentiates both serum withdrawal- and TNF alpha-induced apoptosis, and interacts with prostate-apoptosis-response-4 (Par-4), a well characterized proapoptotic factor, previously linked to prostate cancer and neurodegenerative diseases. We show that endogenous Par-4 colocalizes with ectopic THAP1 within PML NBs in primary endothelial cells and fibroblasts. In addition, we found that Par-4 is a component of PML NBs in blood vessels, a major site of PML expression in vivo. Finally, we investigated the role of the THAP domain in THAP1 activities and found that this putative DNA-binding domain is not required for Par-4 binding and localization within PML NBs, but is essential for THAP1 proapoptotic activity. Together, our results provide an unexpected link between a nuclear factor of the THAP family, the proapoptotic protein Par-4 and PML nuclear bodies.

Pubmed ID: 12717420

Authors

  • Roussigne M
  • Cayrol C
  • Clouaire T
  • Amalric F
  • Girard JP

Journal

Oncogene

Publication Data

April 24, 2003

Associated Grants

None

Mesh Terms

  • Apoptosis
  • Apoptosis Regulatory Proteins
  • Carrier Proteins
  • Cell Nucleus
  • DNA-Binding Proteins
  • Epithelium
  • Fibroblasts
  • Humans
  • Intracellular Signaling Peptides and Proteins
  • Leukemia, Promyelocytic, Acute
  • Neoplasm Proteins
  • Nuclear Proteins
  • Protein Structure, Tertiary
  • Transcription Factors
  • Tumor Suppressor Proteins