SET: a potent inhibitor of protein phosphatase 2A involved in apoptosis, transcription, nucleosome assembly and histone binding. The translocation t(6;9)(q21;q34.1) NUP214/CAN is found in some cases of acute undifferentiated leukemia (AUL). Two alternatively spliced isoforms have been described. Isoform 1 and isoform 2 interact directly with each other and with ANP32A within the tripartite INHAT (inhibitor of acetyltransferases) complex. Both isoforms inhibit the acetylation of histones (HAT) and nucleosomes, most probably by masking the accessibility of lysines of histones to the acetylases. The predominant target for inhibition is histone H4. HAT inhibition leads to silencing of HAT-dependent transcription and prevents active demethylation of DNA. Both isoforms stimulate DNA replication of the adenovirus genome complexed with viral core proteins; however, isoform 2 specific activity is higher. Isoform 2 anti-apoptotic activity is mediated by inhibition of the GZMA-activated DNase, NME1. In the course of cytotoxic T lymphocyte (CTL)-induced apoptosis, GZMA cleaves SET, disrupting its binding to NME1 and releasing NME1 inhibition.
Protein type: Nuclear receptor co-regulator; DNA-binding; Apoptosis; DNA replication; Oncoprotein; Inhibitor
Chromosomal Location of Human Ortholog: 9q34
Cellular Component: nucleoplasm; protein complex; perinuclear region of cytoplasm; endoplasmic reticulum; cytoplasm; cytosol; nucleus
Molecular Function: protein binding; DNA binding; histone binding; protein phosphatase type 2A regulator activity; protein phosphatase inhibitor activity
Biological Process: nucleosome assembly; nucleosome disassembly; regulation of catalytic activity; negative regulation of catalytic activity; nucleocytoplasmic transport; gene expression; negative regulation of neuron apoptosis; mitotic cell cycle; DNA replication; negative regulation of transcription, DNA-dependent; negative regulation of histone acetylation
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