Thirty years of SET/TAF1β/I2PP2A: from the identification of the biological functions to its implications in cancer and Alzheimer's disease.
Antonella Di MambroMaria Teresa EspositoPublished in: Bioscience reports (2022)
The gene encoding for the protein SE translocation (SET) was identified for the first time 30 years ago as part of a chromosomal translocation in a patient affected by leukemia. Since then, accumulating evidence have linked overexpression of SET, aberrant SET splicing, and cellular localization 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.
Keyphrases
- oxidative stress
- cell cycle
- dna repair
- cell death
- dna damage
- genome wide
- papillary thyroid
- cell proliferation
- dna methylation
- gene expression
- transcription factor
- multiple sclerosis
- cognitive decline
- signaling pathway
- spinal cord injury
- young adults
- binding protein
- mild cognitive impairment
- heat shock protein
- protein protein
- diabetic rats