SET nuclear proto-oncogene (SET)

SET nuclear proto-oncogene encodes a multifunctional protein that acts as a potent endogenous inhibitor of protein phosphatase 2A (PP2A), a tumor suppressor enzyme. SET is a subunit of the inhibitor of acetyltransferases (INHAT) complex, modulates chromatin structure by masking histone lysines to inhibit acetylation, and broadly represses gene transcription. SET is expressed in all tissues, with predominant nuclear localization, and can shuttle to the cytoplasm. It interacts directly with key transcription factors (e.g., p53), regulating their acetylation and gene transcriptional activity, particularly controlling cell cycle arrest and apoptosis. Overexpression and mislocalization of SET are implicated in a variety of human cancers, poor clinical outcomes, and resistance to therapy, as well as neurodegenerative disorders such as Alzheimer’s disease and amyotrophic lateral sclerosis. SET plays additional roles in DNA replication, repair, and metabolic regulation.

Other names

2PP2AIGAADMRD58TAF-II2PP2AIPP2A2PHAPIITAF-IBETA

Inhibition of SET relieves its blockade on PP2A activity, promoting the tumor suppressor functions of PP2A (dephosphorylation of oncogenic kinases, induction of cell cycle arrest and apoptosis). - Inhibiting SET can enhance acetylation of histones and transcription factors, restoring gene expression suppressed by SET. - Potential modulation of DNA repair efficiency by altering SET-KU70/80 interactions.