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GLTSCR2 promotes the nucleoplasmic translocation and subsequent degradation of nucleolar ARF

Sun Lee1, Young-Eun Cho1, Sang-Hoon Kim1

  • 1Department of Pathology, College of Medicine, Kyung Hee University, Seoul 130-701, Korea.

Oncotarget
|June 21, 2016
PubMed

Insights

The tumor suppressor p14ARF/ARF moves from the nucleolus to the nucleoplasm, aided by GLTSCR2, promoting its degradation and impacting cell fate.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Oncology

Background:

  • p14ARF/ARF is a tumor suppressor regulating cell fate via p53-dependent or independent pathways.
  • ARF resides in the nucleolus, interacting with nucleoplasmic proteins like p53 and MDM2, posing a localization challenge.
  • GLTSCR2 (PICT-1) is a nucleolar protein implicated in both tumor suppression and oncogenesis.

Purpose of the Study:

  • To investigate the role of GLTSCR2 in regulating the subcellular localization and stability of p14ARF/ARF.
  • To elucidate the mechanism by which GLTSCR2 influences ARF's tumor-suppressive functions.

Main Methods:

  • Co-immunoprecipitation to detect ARF-GLTSCR2 binding.
  • Analysis of ARF translocation from nucleolus to nucleoplasm.
  • Assessment of ARF ubiquitination and degradation mediated by GLTSCR2 and ULF/TRIP12.

Main Results:

  • GLTSCR2 binds to ARF, facilitating its release from the nucleolus to the nucleoplasm.
  • GLTSCR2 enhances ARF binding to the E3 ubiquitin ligase ULF/TRIP12.
  • GLTSCR2 promotes ARF polyubiquitination and subsequent degradation, impacting ARF's tumor suppressor activity.

Conclusions:

  • GLTSCR2 promotes nucleoplasmic translocation and degradation of ARF.
  • GLTSCR2 acts as a key regulator of ARF's subcellular localization and protein stability.
  • These findings highlight GLTSCR2's role in modulating ARF-mediated tumor suppression.
Keywords:
alternative reading framedegradationglioma tumor suppressor candidate region gene 2 proteinsubcellular localizationtranslocation

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