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Cul4A-DDB1–mediated K146 monoubiquitination of PHGDH recruits DNAJA1 to facilitate tetrameric formation of PHGDH, which enhances its enzymatic activity and increases SAM levels. Increased levels of SAM specifically initiate SETD1A-mediated histone H3K4me3 to upregulate LAMC2 and CYR61 expression, thereby promoting tumor cell migration and CRC metastasis. 3-PG, 3-phosphoglycerate; 3-PO, 3-phosphooxypyruvate.
