Thirty years of SET/TAF1β/I2PP2A: from the identification of the biological functions to its implications in cancer and Alzheimer’s disease

• Published in: Bioscience reports Vol. 42; no. 11; p. 1
• Main Authors: Di Mambro, Antonella, Esposito, Maria Teresa
• Format: Journal Article
• Language: English
• Published: New York Portland Press Ltd The Biochemical Society 01.11.2022; Portland Press Ltd
• Subjects: Acetylation; Alzheimer's disease; Apoptosis; Cancer; Cell cycle; Cell Cycle, Growth & Proliferation; Cell death; Cell Death & Injury; Cell differentiation; Cell migration; Cell Migration, Adhesion & Morphology; Chromatin remodeling; Chromosome translocations; Developmental Biology; DNA methylation; DNA repair; Embryology; Epigenetics; Gene deletion; Gene Expression & Regulation; Genes; Histones; Kinases; Leukemia; Localization; Medical prognosis; Molecular Bases of Health & Disease; Molecular biology; Molecular modelling; Neurodegenerative diseases; Neuroscience; Oxidative stress; Pathogenesis; Peptides; Physiology; Protein expression; Protein transport; Protein-serine/threonine phosphatase; Proteins; Review; Spinal cord; Tau protein; Therapeutic targets; Threonine phosphatase; Translocation; Tumorigenesis
• ISSN: 0144-8463; 1573-4935
• DOI: 10.1042/BSR20221280

Abstract 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.