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Structure of p53 DNA-binding domain and ZNF568 KRAB domain complex
Structural highlights
FunctionZN568_HUMAN Has transcriptional repression activity, partially through the recruitment of the corepressor TRIM28 but has also repression activity independently of this interaction. Essential during embryonic development, where it acts as a direct repressor of a placental-specific transcript of IGF2 in early development and regulates convergent extension movements required for axis elongation and tissue morphogenesis in all germ layers. Also important for normal morphogenesis of extraembryonic tissues including the yolk sac, extraembryonic mesoderm and placenta. May enhance proliferation or maintenance of neural stem cells.[UniProtKB:E9PYI1] Publication Abstract from PubMedThe tumor suppressor p53 plays important roles in suppressing the development and progression of cancer by responding to various stress signals. In addition, p53 can regulate the metabolic pathways of cancer cells by regulating energy metabolism and oxidative phosphorylation. Here, we present a mechanism for the interaction between p53 and ZNF568. Initially, we used X-ray crystallography to determine the irregular loop structure of the ZNF568 KRAB domain; this loop plays an important role in the interaction between p53 and ZNF568. In addition, Cryo-EM was used to examine how the p53 DBD and ZNF568 KRAB domains bind together. The function of ZNF568 on p53-mediated mitochondrial respiration was confirmed by measuring glucose consumption and lactate production. These findings show that ZNF568 can reduce p53-mediated mitochondrial respiratory activity by binding to p53 and inhibiting the transcription of SCO2. SIGNIFICANCE: ZNF568 can directly bind to the p53 DBD and transcriptionally regulate the SCO2 gene. SCO2 transcriptional regulation by interaction between ZNF568 and p53 may regulate the balance between mitochondrial respiration and glycolysis. Influence of the interaction between p53 and ZNF568 on mitochondrial oxidative phosphorylation.,Han CW, Jeong MS, Jang SB Int J Biol Macromol. 2024 Aug;275(Pt 2):133314. doi: , 10.1016/j.ijbiomac.2024.133314. Epub 2024 Jun 27. PMID:38944084[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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