Topic
PADI1
About: PADI1 is a research topic. Over the lifetime, 7 publications have been published within this topic receiving 144 citations. The topic is also known as: HPAD10 & PAD1.
Papers
TL;DR: A novel function of PADI1 is revealed during early embryo development transitions by catalyzing histone tail citrullination, which facilitates early embryo genome transactivation.
Abstract: Peptidylarginine deiminase (PADI) enzymes are increasingly being associated with the regulation of chromatin structure and gene activity via histone citrullination. As one of the PADI family members, PADI1 has been mainly reported to be expressed in the epidermis and uterus, where the protein in keratinocytes is thought to promote differentiation by citrullinating filament proteins. However, the roles of PADI1 in preimplantation development have not been addressed. Using a PADI1-specific inhibitor and Padi1-morpholino knockdown, we found that citrullination of histone tails at H4R3 and H3R2/8/17 were markedly reduced in the 2- and 4-cell embryos. Consistent with this observation, early embryo development was also arrested at the 4-cell stage upon depletion of PADI1 or inhibition of PADI1 enzyme activity. Additionally, by employing 5-ethynyl uridine (EU) incorporation analysis, ablation of PADI1 function led to a dramatic decrease in overall transcriptional activity, correlating well with the reduced levels of phosphorylation of RNA Pol II at Ser2 observed at 2- or 4-cell stage of embryos under Padi1 knockdown or inhibiting PADI1. Thus, our data reveal a novel function of PADI1 during early embryo development transitions by catalyzing histone tail citrullination, which facilitates early embryo genome transactivation.
49 citations
TL;DR: Using quantitative reverse transcription-PCR experiments, it is shown that PADI1 mRNAs are more abundant in keratinocytes cultured with 1.2 than 0.15 mM calcium, and data indicate that MZF1 and Sp1/Sp3 binding to the promoter region drive the P ADI1 expression.
38 citations
TL;DR: The molecular bases of the expression specificity of PADI1 and PADi3 during keratinocyte differentiation through a long-range enhancer are revealed and support a model of P ADI gene regulation depending on c-Jun-JunD competition.
27 citations
TL;DR: Citrullination of arginine 106 in the glycolytic enzyme pyruvate kinase M2 modulating its allosteric regulation, gly colysis and cancer cell proliferation is studied.
Abstract: Conversion of peptidyl-arginine to peptidyl citrulline, known as citrullination, is a post-translational protein modification catalyzed by the PADI (Protein Arginine Deiminase) family of enzymes. PADI1 and PADI3 catalyze citrullination of arginine 106 in the glycolytic enzyme pyruvate kinase M2 modulating its allosteric regulation, glycolysis and cancer cell proliferation.
4 citations
TL;DR: In this paper, it was shown that the conversion of arginines to citrulline impacts key interactions within PKM2 that act in concert to reprogramme its activity as an additional mechanism regulating this important enzyme.
Abstract: Chromodomain helicase DNA binding protein 4 (CHD4) is an ATPase subunit of the Nucleosome Remodelling and Deacetylation (NuRD) complex that regulates gene expression. CHD4 is essential for growth of multiple patient derived melanoma xenografts and for breast cancer. Here we show that CHD4 regulates expression of PADI1 (Protein Arginine Deiminase 1) and PADI3 in multiple cancer cell types modulating citrullination of arginine residues of the allosterically-regulated glycolytic enzyme pyruvate kinase M2 (PKM2). Citrullination of PKM2 R106 reprogrammes cross-talk between PKM2 ligands lowering its sensitivity to the inhibitors Tryptophan, Alanine and Phenylalanine and promoting activation by Serine. Citrullination thus bypasses normal physiological regulation by low Serine levels to promote excessive glycolysis and reduced cell proliferation. We further show that PADI1 and PADI3 expression is up-regulated by hypoxia where PKM2 citrullination contributes to increased glycolysis. We provide insight as to how conversion of arginines to citrulline impacts key interactions within PKM2 that act in concert to reprogramme its activity as an additional mechanism regulating this important enzyme.
2 citations
Related Topics (5)
Performance Metrics
| Year | Papers |
|---|---|
| 2021 | 2 |
| 2016 | 1 |
| 2010 | 1 |
| 2009 | 1 |
| 2008 | 2 |