Anastasia Mpakali

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AIMS Vascular endothelial growth factors C and D (VEGF-C and VEGF-D) play a major role in lymphangiogenesis and activate VEGF receptor 3 (VEGFR-3). Our purpose was to study the clinicopathologic and clinical value of VEGF-C, VEGF-D and VEGFR-3 in invasive breast carcinoma. MATERIAL AND METHODS Immunohistochemistry was performed in paraffin-embedded tissue(More)
Aminopeptidases that generate antigenic peptides influence immunodominance and adaptive cytotoxic immune responses. The mechanisms that allow these enzymes to efficiently process a vast number of different long peptide substrates are poorly understood. In this work, we report the structure of insulin-regulated aminopeptidase, an enzyme that prepares(More)
Dnmt3a1 and Dnmt3a2 are two de novo DNA methyltransferases expressed in mouse embryonic stem cells (mESCs). They differ in that a 219-amino-acid (aa) amino (N)-terminal noncatalytic domain is present only in Dnmt3a1. Here, we examined the unique functions of Dnmt3a1 in mESCs by targeting the coding sequence of the Dnmt3a1 N-terminal domain tagged with(More)
Endoplasmic reticulum (ER) aminopeptidases process antigenic peptide precursors to generate epitopes for presentation by MHC class I molecules and help shape the antigenic peptide repertoire and cytotoxic T-cell responses. To perform this function, ER aminopeptidases have to recognize and process a vast variety of peptide sequences. To understand how these(More)
Endoplasmic reticulum aminopeptidase 1 (ERAP1) is an intracellular enzyme that is important for the generation of antigenic epitopes and major histocompatibility class I-restricted adaptive immune responses. ERAP1 processes a vast variety of different peptides but still shows length and sequence selectivity, although the mechanism behind these properties is(More)
Insulin-regulated aminopeptidase (IRAP) is an enzyme with several important biological functions that is known to process a large variety of different peptidic substrates, although the mechanism behind this wide specificity is not clearly understood. We describe a crystal structure of IRAP in complex with a recently developed bioactive and selective(More)
Endoplasmic reticulum aminopeptidase 2 assists with the generation of antigenic peptides for presentation onto Major Histocompatibility Class I molecules in humans. Recent evidence has suggested that the activity of ERAP2 may contribute to the generation of autoimmunity, thus making ERAP2 a possible pharmacological target for the regulation of adaptive(More)
The oxytocinase subfamily of M1 aminopeptidases, consisting of ER aminopeptidase 1 (ERAP1), ER aminopeptidase 2 (ERAP2), and insulin-regulated aminopeptidase (IRAP), plays critical roles in the generation of antigenic peptides and indirectly regulates human adaptive immune responses. We have previously demonstrated that phosphinic pseudotripeptides can(More)
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