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

Myriam Roussigne1, Corinne Cayrol, Thomas Clouaire

  • 1Laboratoire de Biologie Vasculaire, Institut de Pharmacologie et de Biologie Structurale, CNRS UMR 5089, 205 route de Narbonne, 31077 Toulouse, France.

Oncogene
|April 30, 2003
PubMed

Insights

THAP1, a novel nuclear factor, interacts with the proapoptotic protein Par-4 and localizes to Promyelocytic Leukemia (PML) nuclear bodies, enhancing apoptosis. The THAP domain is crucial for THAP1

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Cancer Research

Background:

  • Promyelocytic leukemia (PML) nuclear bodies (PML NBs) are key subnuclear structures regulated by the PML tumor suppressor.
  • THAP proteins represent a novel family of cellular factors with a conserved THAP domain.

Purpose of the Study:

  • To investigate the role of THAP1, a member of the THAP protein family, in apoptosis.
  • To determine the association of THAP1 with PML NBs and its interaction with the proapoptotic factor Par-4.

Main Methods:

  • Immunofluorescence microscopy to assess colocalization of THAP1 and Par-4 within PML NBs.
  • Western blotting and co-immunoprecipitation to confirm protein interactions.
  • Functional assays to evaluate the role of the THAP domain in THAP1's proapoptotic activity.

Main Results:

  • THAP1 was identified as a novel nuclear proapoptotic factor that localizes to PML NBs.
  • THAP1 interacts with and colocalizes with Par-4 within PML NBs in various cell types and in vivo.
  • The THAP domain is essential for THAP1's proapoptotic function but not for Par-4 binding or PML NB localization.

Conclusions:

  • THAP1 links the THAP protein family to PML NBs and the proapoptotic protein Par-4.
  • This interaction potentiates apoptosis, suggesting a novel pathway involving THAP1, Par-4, and PML NBs in cancer and other diseases.
  • The THAP domain's role highlights a specific mechanism for THAP1-mediated apoptosis.

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