Gene interactions and pathways from curated databases and text-mining
Mol Cell 2007, PMID: 17707234

Modulation of p53 function by SET8-mediated methylation at lysine 382.

Shi, Xiaobing; Kachirskaia, Ioulia; Yamaguchi, Hiroshi; West, Lisandra E; Wen, Hong; Wang, Evelyn W; Dutta, Sucharita; Appella, Ettore; Gozani, Or

Reversible covalent methylation of lysine residues on histone proteins constitutes a principal molecular mechanism that links chromatin states to diverse biological outcomes. Recently, lysine methylation has been observed on nonhistone proteins, suggesting broad cellular roles for the enzymes generating and removing methyl moieties. Here we report that the lysine methyltransferase enzyme SET8/PR-Set7 regulates the tumor suppressor protein p53. We find that SET8 specifically monomethylates p53 at lysine 382 (p53K382me1). This methylation event robustly suppresses p53-mediated transcription activation of highly responsive target genes but has little influence on weak targets. Further, depletion of SET8 augments the proapoptotic and checkpoint activation functions of p53, and accordingly, SET8 expression is downregulated upon DNA damage. Together, our study identifies SET8 as a p53-modifying enzyme, identifies p53K382me1 as a regulatory posttranslational modification of p53, and begins to dissect how methylation may contribute to a dynamic posttranslational code that modulates distinct p53 functions.

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Text Mining Data

p53 → SET8/PR-Set7: " Here we report that the lysine methyltransferase enzyme SET8/PR-Set7 regulates the tumor suppressor protein p53 "

p53 → SET8/PR-Set7: " Here we report that the lysine methyltransferase enzyme SET8/PR-Set7 regulates the tumor suppressor protein p53 "

Manually curated Databases

  • IRef Biogrid Interaction: SETD8 — TP53 (direct interaction, enzymatic study)
  • NCI Pathway Database Direct p53 effectors: GCN5-L/ADA2B/TAF9 complex (KAT2A-TADA2B-TAF9) → HDAC2 (HDAC2) (transcription, activates)
    Evidence: mutant phenotype, reporter gene, physical interaction
  • NCI Pathway Database Direct p53 effectors: GCN5-L/ADA2B/TAF9 complex (KAT2A-TADA2B-TAF9) → POU4F1 (POU4F1) (transcription, activates)
    Evidence: mutant phenotype, reporter gene, physical interaction
  • NCI Pathway Database Direct p53 effectors: GCN5-L/ADA2B/TAF9 complex (KAT2A-TADA2B-TAF9) → BRG1 (SMARCA4) (transcription, activates)
    Evidence: mutant phenotype, reporter gene, physical interaction
  • NCI Pathway Database Direct p53 effectors: GCN5-L/ADA2B/TAF9 complex (KAT2A-TADA2B-TAF9) → HZF (ZNF385A) (transcription, activates)
    Evidence: mutant phenotype, reporter gene, physical interaction
  • NCI Pathway Database Direct p53 effectors: GCN5-L/ADA2B/TAF9 complex (KAT2A-TADA2B-TAF9) → p21CIP1 (CDKN1A) (transcription, activates)
    Evidence: mutant phenotype, reporter gene, physical interaction
  • NCI Pathway Database Direct p53 effectors: GCN5-L/ADA2B/TAF9 complex (KAT2A-TADA2B-TAF9) → p53 (tetramer) complex (TP53) (transcription, activates)
    Evidence: mutant phenotype, reporter gene, physical interaction
  • NCI Pathway Database Direct p53 effectors: HDAC2 (HDAC2) → POU4F1 (POU4F1) (transcription, inhibits)
    Evidence: mutant phenotype, reporter gene, physical interaction
  • NCI Pathway Database Direct p53 effectors: HDAC2 (HDAC2) → BRG1 (SMARCA4) (transcription, inhibits)
    Evidence: mutant phenotype, reporter gene, physical interaction
  • NCI Pathway Database Direct p53 effectors: HDAC2 (HDAC2) → HZF (ZNF385A) (transcription, inhibits)
    Evidence: mutant phenotype, reporter gene, physical interaction
  • NCI Pathway Database Direct p53 effectors: HDAC2 (HDAC2) → p21CIP1 (CDKN1A) (transcription, inhibits)
    Evidence: mutant phenotype, reporter gene, physical interaction
  • NCI Pathway Database Direct p53 effectors: HDAC2 (HDAC2) → p53 (tetramer) complex (TP53) (transcription, inhibits)
    Evidence: mutant phenotype, reporter gene, physical interaction
  • NCI Pathway Database Direct p53 effectors: POU4F1 (POU4F1) → BRG1 (SMARCA4) (transcription, activates)
    Evidence: mutant phenotype, reporter gene, physical interaction
  • NCI Pathway Database Direct p53 effectors: POU4F1 (POU4F1) → HZF (ZNF385A) (transcription, activates)
    Evidence: mutant phenotype, reporter gene, physical interaction
  • NCI Pathway Database Direct p53 effectors: POU4F1 (POU4F1) → p21CIP1 (CDKN1A) (transcription, activates)
    Evidence: mutant phenotype, reporter gene, physical interaction
  • NCI Pathway Database Direct p53 effectors: POU4F1 (POU4F1) → p53 (tetramer) complex (TP53) (transcription, activates)
    Evidence: mutant phenotype, reporter gene, physical interaction
  • NCI Pathway Database Direct p53 effectors: BRG1 (SMARCA4) → HZF (ZNF385A) (transcription, activates)
    Evidence: mutant phenotype, reporter gene, physical interaction
  • NCI Pathway Database Direct p53 effectors: BRG1 (SMARCA4) → p21CIP1 (CDKN1A) (transcription, activates)
    Evidence: mutant phenotype, reporter gene, physical interaction
  • NCI Pathway Database Direct p53 effectors: BRG1 (SMARCA4) → p53 (tetramer) complex (TP53) (transcription, activates)
    Evidence: mutant phenotype, reporter gene, physical interaction
  • NCI Pathway Database Direct p53 effectors: HZF (ZNF385A) → p21CIP1 (CDKN1A) (transcription, activates)
    Evidence: mutant phenotype, reporter gene, physical interaction
  • NCI Pathway Database Direct p53 effectors: HZF (ZNF385A) → p53 (tetramer) complex (TP53) (transcription, activates)
    Evidence: mutant phenotype, reporter gene, physical interaction
  • NCI Pathway Database Direct p53 effectors: GCN5-L/ADA2B/TAF9 complex (KAT2A-TADA2B-TAF9) → HDAC2 (HDAC2) (transcription, activates)
    Evidence: mutant phenotype, reporter gene, physical interaction
  • NCI Pathway Database Direct p53 effectors: GCN5-L/ADA2B/TAF9 complex (KAT2A-TADA2B-TAF9) → POU4F1 (POU4F1) (transcription, activates)
    Evidence: mutant phenotype, reporter gene, physical interaction
  • NCI Pathway Database Direct p53 effectors: GCN5-L/ADA2B/TAF9 complex (KAT2A-TADA2B-TAF9) → BRG1 (SMARCA4) (transcription, activates)
    Evidence: mutant phenotype, reporter gene, physical interaction
  • NCI Pathway Database Direct p53 effectors: GCN5-L/ADA2B/TAF9 complex (KAT2A-TADA2B-TAF9) → HZF (ZNF385A) (transcription, activates)
    Evidence: mutant phenotype, reporter gene, physical interaction
  • NCI Pathway Database Direct p53 effectors: GCN5-L/ADA2B/TAF9 complex (KAT2A-TADA2B-TAF9) → p21CIP1 (CDKN1A) (transcription, activates)
    Evidence: mutant phenotype, reporter gene, physical interaction
  • NCI Pathway Database Direct p53 effectors: GCN5-L/ADA2B/TAF9 complex (KAT2A-TADA2B-TAF9) → p53 (tetramer) complex (TP53) (transcription, activates)
    Evidence: mutant phenotype, reporter gene, physical interaction
  • NCI Pathway Database Direct p53 effectors: HDAC2 (HDAC2) → POU4F1 (POU4F1) (transcription, inhibits)
    Evidence: mutant phenotype, reporter gene, physical interaction
  • NCI Pathway Database Direct p53 effectors: HDAC2 (HDAC2) → BRG1 (SMARCA4) (transcription, inhibits)
    Evidence: mutant phenotype, reporter gene, physical interaction
  • NCI Pathway Database Direct p53 effectors: HDAC2 (HDAC2) → HZF (ZNF385A) (transcription, inhibits)
    Evidence: mutant phenotype, reporter gene, physical interaction
  • NCI Pathway Database Direct p53 effectors: HDAC2 (HDAC2) → p21CIP1 (CDKN1A) (transcription, inhibits)
    Evidence: mutant phenotype, reporter gene, physical interaction
  • NCI Pathway Database Direct p53 effectors: HDAC2 (HDAC2) → p53 (tetramer) complex (TP53) (transcription, inhibits)
    Evidence: mutant phenotype, reporter gene, physical interaction
  • NCI Pathway Database Direct p53 effectors: POU4F1 (POU4F1) → BRG1 (SMARCA4) (transcription, activates)
    Evidence: mutant phenotype, reporter gene, physical interaction
  • NCI Pathway Database Direct p53 effectors: POU4F1 (POU4F1) → HZF (ZNF385A) (transcription, activates)
    Evidence: mutant phenotype, reporter gene, physical interaction
  • NCI Pathway Database Direct p53 effectors: POU4F1 (POU4F1) → p21CIP1 (CDKN1A) (transcription, activates)
    Evidence: mutant phenotype, reporter gene, physical interaction
  • NCI Pathway Database Direct p53 effectors: POU4F1 (POU4F1) → p53 (tetramer) complex (TP53) (transcription, activates)
    Evidence: mutant phenotype, reporter gene, physical interaction
  • NCI Pathway Database Direct p53 effectors: BRG1 (SMARCA4) → HZF (ZNF385A) (transcription, activates)
    Evidence: mutant phenotype, reporter gene, physical interaction
  • NCI Pathway Database Direct p53 effectors: BRG1 (SMARCA4) → p21CIP1 (CDKN1A) (transcription, activates)
    Evidence: mutant phenotype, reporter gene, physical interaction
  • NCI Pathway Database Direct p53 effectors: BRG1 (SMARCA4) → p53 (tetramer) complex (TP53) (transcription, activates)
    Evidence: mutant phenotype, reporter gene, physical interaction
  • NCI Pathway Database Direct p53 effectors: HZF (ZNF385A) → p21CIP1 (CDKN1A) (transcription, activates)
    Evidence: mutant phenotype, reporter gene, physical interaction
  • NCI Pathway Database Direct p53 effectors: HZF (ZNF385A) → p53 (tetramer) complex (TP53) (transcription, activates)
    Evidence: mutant phenotype, reporter gene, physical interaction
  • NCI Pathway Database Direct p53 effectors: GCN5-L/ADA2B/TAF9 complex (KAT2A-TADA2B-TAF9) → SP1 (SP1) (transcription, activates)
    Evidence: mutant phenotype, reporter gene, physical interaction
  • NCI Pathway Database Direct p53 effectors: GCN5-L/ADA2B/TAF9 complex (KAT2A-TADA2B-TAF9) → p53 (tetramer) complex (TP53) (transcription, activates)
    Evidence: mutant phenotype, reporter gene, physical interaction
  • NCI Pathway Database Direct p53 effectors: GCN5-L/ADA2B/TAF9 complex (KAT2A-TADA2B-TAF9) → SLUG (SNAI2) (transcription, activates)
    Evidence: mutant phenotype, reporter gene, physical interaction
  • NCI Pathway Database Direct p53 effectors: SP1 (SP1) → p53 (tetramer) complex (TP53) (transcription, activates)
    Evidence: mutant phenotype, reporter gene, physical interaction
  • NCI Pathway Database Direct p53 effectors: SP1 (SP1) → SLUG (SNAI2) (transcription, activates)
    Evidence: mutant phenotype, reporter gene, physical interaction
  • NCI Pathway Database Direct p53 effectors: p53 (tetramer) complex (TP53) → SLUG (SNAI2) (transcription, activates)
    Evidence: mutant phenotype, reporter gene, physical interaction
  • NCI Pathway Database Direct p53 effectors: GCN5-L/ADA2B/TAF9 complex (KAT2A-TADA2B-TAF9) → HDAC2 (HDAC2) (transcription, activates)
    Evidence: mutant phenotype, reporter gene, physical interaction
  • NCI Pathway Database Direct p53 effectors: GCN5-L/ADA2B/TAF9 complex (KAT2A-TADA2B-TAF9) → POU4F1 (POU4F1) (transcription, activates)
    Evidence: mutant phenotype, reporter gene, physical interaction
  • NCI Pathway Database Direct p53 effectors: GCN5-L/ADA2B/TAF9 complex (KAT2A-TADA2B-TAF9) → BRG1 (SMARCA4) (transcription, activates)
    Evidence: mutant phenotype, reporter gene, physical interaction
  • NCI Pathway Database Direct p53 effectors: GCN5-L/ADA2B/TAF9 complex (KAT2A-TADA2B-TAF9) → HZF (ZNF385A) (transcription, activates)
    Evidence: mutant phenotype, reporter gene, physical interaction
  • NCI Pathway Database Direct p53 effectors: GCN5-L/ADA2B/TAF9 complex (KAT2A-TADA2B-TAF9) → p21CIP1 (CDKN1A) (transcription, activates)
    Evidence: mutant phenotype, reporter gene, physical interaction
  • NCI Pathway Database Direct p53 effectors: GCN5-L/ADA2B/TAF9 complex (KAT2A-TADA2B-TAF9) → p53 (tetramer) complex (TP53) (transcription, activates)
    Evidence: mutant phenotype, reporter gene, physical interaction
  • NCI Pathway Database Direct p53 effectors: HDAC2 (HDAC2) → POU4F1 (POU4F1) (transcription, inhibits)
    Evidence: mutant phenotype, reporter gene, physical interaction
  • NCI Pathway Database Direct p53 effectors: HDAC2 (HDAC2) → BRG1 (SMARCA4) (transcription, inhibits)
    Evidence: mutant phenotype, reporter gene, physical interaction
  • NCI Pathway Database Direct p53 effectors: HDAC2 (HDAC2) → HZF (ZNF385A) (transcription, inhibits)
    Evidence: mutant phenotype, reporter gene, physical interaction
  • NCI Pathway Database Direct p53 effectors: HDAC2 (HDAC2) → p21CIP1 (CDKN1A) (transcription, inhibits)
    Evidence: mutant phenotype, reporter gene, physical interaction
  • NCI Pathway Database Direct p53 effectors: HDAC2 (HDAC2) → p53 (tetramer) complex (TP53) (transcription, inhibits)
    Evidence: mutant phenotype, reporter gene, physical interaction
  • NCI Pathway Database Direct p53 effectors: POU4F1 (POU4F1) → BRG1 (SMARCA4) (transcription, activates)
    Evidence: mutant phenotype, reporter gene, physical interaction
  • NCI Pathway Database Direct p53 effectors: POU4F1 (POU4F1) → HZF (ZNF385A) (transcription, activates)
    Evidence: mutant phenotype, reporter gene, physical interaction
  • NCI Pathway Database Direct p53 effectors: POU4F1 (POU4F1) → p21CIP1 (CDKN1A) (transcription, activates)
    Evidence: mutant phenotype, reporter gene, physical interaction
  • NCI Pathway Database Direct p53 effectors: POU4F1 (POU4F1) → p53 (tetramer) complex (TP53) (transcription, activates)
    Evidence: mutant phenotype, reporter gene, physical interaction
  • NCI Pathway Database Direct p53 effectors: BRG1 (SMARCA4) → HZF (ZNF385A) (transcription, activates)
    Evidence: mutant phenotype, reporter gene, physical interaction
  • NCI Pathway Database Direct p53 effectors: BRG1 (SMARCA4) → p21CIP1 (CDKN1A) (transcription, activates)
    Evidence: mutant phenotype, reporter gene, physical interaction
  • NCI Pathway Database Direct p53 effectors: BRG1 (SMARCA4) → p53 (tetramer) complex (TP53) (transcription, activates)
    Evidence: mutant phenotype, reporter gene, physical interaction
  • NCI Pathway Database Direct p53 effectors: HZF (ZNF385A) → p21CIP1 (CDKN1A) (transcription, activates)
    Evidence: mutant phenotype, reporter gene, physical interaction
  • NCI Pathway Database Direct p53 effectors: HZF (ZNF385A) → p53 (tetramer) complex (TP53) (transcription, activates)
    Evidence: mutant phenotype, reporter gene, physical interaction
  • NCI Pathway Database Direct p53 effectors: GCN5-L/ADA2B/TAF9 complex (KAT2A-TADA2B-TAF9) → SP1 (SP1) (transcription, activates)
    Evidence: mutant phenotype, reporter gene, physical interaction
  • NCI Pathway Database Direct p53 effectors: GCN5-L/ADA2B/TAF9 complex (KAT2A-TADA2B-TAF9) → p53 (tetramer) complex (TP53) (transcription, activates)
    Evidence: mutant phenotype, reporter gene, physical interaction
  • NCI Pathway Database Direct p53 effectors: GCN5-L/ADA2B/TAF9 complex (KAT2A-TADA2B-TAF9) → SLUG (SNAI2) (transcription, activates)
    Evidence: mutant phenotype, reporter gene, physical interaction
  • NCI Pathway Database Direct p53 effectors: SP1 (SP1) → p53 (tetramer) complex (TP53) (transcription, activates)
    Evidence: mutant phenotype, reporter gene, physical interaction
  • NCI Pathway Database Direct p53 effectors: SP1 (SP1) → SLUG (SNAI2) (transcription, activates)
    Evidence: mutant phenotype, reporter gene, physical interaction
  • NCI Pathway Database Direct p53 effectors: p53 (tetramer) complex (TP53) → SLUG (SNAI2) (transcription, activates)
    Evidence: mutant phenotype, reporter gene, physical interaction
In total, 45 gene pairs are associated to this article in curated databases