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ChIP and RNAseq integrated analysis indicated that the decreased protein level of PKM2 was independent of PKM2 transcription, and LHPP did not reprogram transcription level of metabolic genome. Co-IP and immunofluorescence assay manifested that LHPP interacted with PKM2, and this interaction interfered the protein stability, then induced ubiquitin-mediated degradation of PKM2. Rescue assay confirmed that restoring the expression of PKM2 effectively reversed the restrained energy metabolism and the inhibited cancer cell growth caused by