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. 2024 Dec 27;13:RP92741. doi: 10.7554/eLife.92741

Figure 3. TIPE promotes HIF-1α transcription in a PKM2-dependent manner.

Figure 3.

(A) Proposed molecular mechanism by which dimeric PKM2 regulates cell proliferation and glycolysis by modulating HIF-1α activity. (B) TIPE, especially when combined with PKM2, boosts relative hypoxia response element (HRE) luciferase activity, as examined by luciferase reporter assay. (C) TIPE promoted HRE activity in a dose- and PKM2-dependent manner. (D, E) TIPE increases HIF-1α targeted genes, including LDHA and SLC2A1, in a dose- and PKM2-dependent manner. (F, G) TIPE promoted endogenous interaction between PKM2 and HIF-1α in melanoma cells using a Doulink assay. Interference of TIPE in A375 cells promoted the interaction between PKM2 and HIF-1α (upper) compared to that overexpression of TIPE in G361 cells decreased their interaction (lower). The density of the red color signaling means the interactive strength between PKM2 and HIF-1α affected by TIPE. (H) TIPE enhanced the PKM2/HIF1a interaction in the nucleus. (I) TIPE increased the exogenous interaction between PKM2 and HIF-1α in a dose- dependent manner in HEK-293T cells. (J) TCGA dataset revealed that TIPE has a positive relationship with hypoxia score in melanoma. (K) Higher expression of TIPE is associated with a relatively higher hypoxia score in melanoma. *p < 0.05; **p < 0.01; ***p < 0.001. The data represent the means ± SEM of three replicates *p<0.05.

Figure 3—source data 1. Original files for western blot analysis displayed in Figure 3.
Figure 3—source data 2. PDF file containing original western blots for Figure 3, indicating the relevant bands and treatments.