SET
Description
The SET (SET nuclear proto-oncogene) is a protein-coding gene located on chromosome 9.
The human gene SET encodes a protein involved in apoptosis, transcription, nucleosome assembly, and histone chaperoning. It is known by various names including HLA-DR-associated protein II, Inhibitor of granzyme A-activated DNase, PHAPII, Phosphatase 2A inhibitor I2PP2A, and Template-activating factor I. SET exists as two isoforms, both of which inhibit protein phosphatase 2A and histone acetylation, contributing to transcriptional silencing. Isoform 2 specifically inhibits apoptosis by blocking the activity of NME1 DNase. SET interacts with various proteins, including those involved in viral infection, suggesting its role in cellular responses to pathogens.
SET protein plays a multifaceted role in cellular processes, including apoptosis, transcription, nucleosome assembly, and histone chaperoning. Isoform 2 inhibits apoptosis by preventing the activation of NME1 DNase through GZMA cleavage, while both isoforms strongly inhibit protein phosphatase 2A. Isoforms 1 and 2 suppress histone acetylation by EP300/CREBBP and PCAF, likely by blocking access to lysine residues, primarily targeting histone H4. This inhibition silences HAT-dependent transcription and hinders DNA demethylation. Interestingly, both isoforms enhance adenovirus DNA replication, with isoform 2 exhibiting greater activity.
SET is also known as 2PP2A, I2PP2A, IGAAD, IPP2A2, MRD58, PHAPII, TAF-I, TAF-IBETA.
