TP53 stimulates IKBIP gene expression

Stable Identifier
R-HSA-9749487
Type
Reaction [omitted]
Species
Homo sapiens
Compartment
ReviewStatus
5/5
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Inhibitor of nuclear factor kappa-B kinase-interacting protein (IKBIP or IKIP) and apoptotic protease-activating factor 1 (APAF1) share a common promoter which coordinates expression of two genes in opposite directions (Hofer-Warbinek R et al. 2004). Expression of APAF1 was shown to be regulated by transcription factor TP53 (p53) which binds to the p53 response element in the promoter of the APAF1 gene (Robles et al. 2001; Fortin A et al. 2001). Like APAF1, expression of endogenous IKBIP was enhanced in human umbilical vein endothelial cells (HUVECs) following X-irradiation. Irradiated cells are known to accumulate TP53, which mediates the response to radiation. Overexpression of TP53 in human embryonic kidney (HEK293) cells increased IKBIP1 protein levels in a dose-dependent manner (Hofer-Warbinek R et al. 2004). Further, knockdown of TP53 by siRNA significantly reduced the level of endogenous IKBIP protein in X-irradiated human osteogenic sarcoma cell lines (U-2 OS). These data suggest that the expression of IKBIP is regulated by TP53. Northern blot analysis using an IKBIP1-specific cDNA probe showed expression of IKBIP in the human lung, kidney, spleen, thymus and skeletal muscle. Fluorescence microscopy analysis revealed that IKBIP localizes to the endoplasmic reticulum (Hofer-Warbinek R et al. 2004; Wu H et al. 2020). Overexpression of IKBIP was found to promote cell death in HUVECs and U-2 OS cells (Hofer-Warbinek R et al. 2004). In addition, IKBIP negatively regulated TLR-induced activation of the transcription factor NF-kappa-B in human and mouse cells (Wu H et al. 2020).
Literature References
PubMed ID Title Journal Year
15389287 A highly conserved proapoptotic gene, IKIP, located next to the APAF1 gene locus, is regulated by p53

Winsauer, G, Orel, L, Schmid, JA, Binder, BR, de Martin, R, Hofer-Warbinek, R, Wiesner, Ch, Mayer, H, Mueller, B

Cell Death Differ 2004
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