Thirty years of SET/TAF1Beta/I2PP2A: From the identification of the biological functions to its implications in cancer and Alzheimer's disease

Antonella Di Mambro, Maria Teresa Esposito

Research output: Contribution to journalArticlepeer-review


The gene encoding for the protein SET was identified for the first time thirty years ago as part of a chromosomal translocation in a patient affected by leukemia. Since then, accumulating evidence have linked over -expression of SET, aberrant SET splicing, and cellular localisation to cancer progression and development of neurodegenerative tauopathies such as Alzheimer's disease. Molecular biology tools, such as targeted genetic deletion, and pharmacological approaches based on SET antagonist peptides, have contributed to unveil the molecular functions of SET and its implications in human pathogenesis. In this review we provide an overview of the functions of SET as inhibitor of histone and non-histone protein acetylation and as a potent endogenous inhibitor of Serine-Threonine phosphatase PP2A. We discuss the role of SET in multiple cellular processes, including chromatin remodelling and gene transcription, DNA repair, oxidative stress, cell cycle, apoptosis cell migration and differentiation. We review the molecular mechanisms linking SET dysregulation to tumorigenesis and discuss how SET commits neurons to progressive cell death in Alzheimer's disease, highlighting the rationale of exploiting SET as a therapeutic target for cancer and neurodegenerative tauopathies.

Original languageEnglish
JournalBioscience reports
Early online date8 Nov 2022
Publication statusE-pub ahead of print - 8 Nov 2022


  • SET
  • I2PP2A
  • leukemia
  • PP2A
  • TAF1beta
  • cancer
  • Alzheimer Disease
  • phosphatase

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