PML/RARa inhibits PTEN expression in hematopoietic cells by competing with PU.1 transcriptional activity

Nélida Inés Noguera, Maria Liliana Piredda, Riccardo Taulli, Gianfranco Catalano, Giulia Angelini, Girish Gaur, Clara Nervi, Maria Teresa Voso, Andrea Lunardi, Pier Paolo Pandolfi, Francesco Lo-Coco

Research output: Contribution to journalArticlepeer-review

Abstract

Acute promyelocitic leukemia (APL) is characterized by the pathognomonic presence in leukemic blasts of the hybrid protein PML/RARA, that acts as a transcriptional repressor impairing the expression of genes that are critical to myeloid differentiation. Here, we show that primary blasts from APL patients express lower levels of the oncosuppressor protein PTEN, as compared to blast cells from other AML subtypes or normal bone marrow, and demonstrate that PML-RARA directly inhibits PTEN expression. We show that All-Trans Retinoic Acid (ATRA) triggers in APL cells an active chromatin status at the core regulatory region of the PTEN promoter, that allows the binding of the myeloid-regulating transcription factor PU.1, and, in turn, the transcriptional induction of PTEN. ATRA, via PML/RARA degradation, also promotes PTEN nuclear re-localization and decreases expression of the PTEN target Aurora A kinase. In conclusion, our findings support the notion that PTEN is one of the primary targets of PML/RARA in APL.

Original languageEnglish
Pages (from-to)66386-66397
Number of pages12
JournalOncotarget
Volume7
Issue number41
DOIs
Publication statusPublished - 2016

Keywords

  • Oncosuppressor
  • PML-RARA
  • PTEN
  • PU.1

ASJC Scopus subject areas

  • Oncology

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