Details

Autor(en) / Beteiligte

• Mikołajczyk, Krzysztof
• Kaczmarek, Radosław
• Czerwiński, Marcin

Titel

Can mutations in the gene encoding transcription factor EKLF (Erythroid Krüppel-Like Factor) protect us against infectious and parasitic diseases?

Ist Teil von

• Postȩpy higieny i medycyny doświadczalnej, 2016-10, Vol.70, p.1068-1086

Ort / Verlag

Poland

Erscheinungsjahr

2016

Quelle

MEDLINE

Beschreibungen/Notizen

• Transcription factor EKLF (Erythroid Krüppel-Like Factor) belongs to the group of Krüppellike factors, which regulate proliferation, differentiation, development and apoptosis of mammalian cells. EKLF factor is present in erythroid cells, where it participates in regulation of hematopoiesis, expression of genes encoding transmembrane proteins (including blood group antigens), and heme biosynthesis enzymes. It is also a key factor in downregulation of γ-globins and activation of β-globin gene expression. The EKLF factor consists of two domains: proline-rich transactivation domain and DNA-binding domain containing three zinc finger motifs, which recognize DNA. EKLF can act as a transcription activator (for example in the case of β-globin gene) or repressor, which depends on the type of posttranslational modification (phosphorylation, SUMOylation, ubiquitination and acetylation). Mutations in the gene encoding EKLF may cause hemoglobinopathies, such as hereditary persistence of fetal hemoglobin and β-thalassemia intermedia, and congenital dyserythropoietic anemia type IV, which is a hematopoietic disorder. These changes may impede invasion of red blood cells by malaria merozoites and cause faster removal of invaded erythrocytes. In addition, mutations in KLF1 may decrease the number of erythrocyte surface antigens that belong to blood group systems such as MN, P1PK, Lutheran, Duffy, Diego and OK. Such antigens can be receptors for protozoans (such as Plasmodium falciparum or Plasmodium vivax), bacteria (like uropathogenic strains of Escherichia coli, Neisseria meningitidis), and toxins (Shiga toxins), which may cause several dangerous diseases including malaria, pyelonephritis, hemorrhagic colitis, hemolytic uremic syndrome (HUS) and meningitis. Here, we propose a hypothesis on possible liaisons between mutations in the gene encoding EKLF and resistance to pathogens.