Author/Editor		Drožina, Gorazd
Title		Vloga posttranslacijskih modifikacij CIITA pri prepisovanju genov MHC II
Type		monografija
Place		Ljubljana
Publisher		Medicinska fakulteta
Publication year		2007
Volume		str. 80
Language		slo
Abstract		Innate and adaptive immunity are connected via antigen processing and presentation, which results in the presentation of antigenic peptides to T cells in the complex with the major histocompatibility (MHC) determinants. MHC class II (MHC II) determinants present antigens to CD4+ T cells, which are the main regulators of the immune response. Their genes are transcribed from compact promoters that form first the MHC II enhanceosome, which contains DNA-bound activators and then the MHC II transcriptosome with the addition of the class II transactivator (CIITA). CIITA is expressed constitutively in dendritic cells and mature B cells and is inducible in most other cell types. Three isoforms of CIITA exist, depending on cell type and inducing signals. CIITA is regulated at the levels of transcription and post-translational modifications. In macrophages, the expression of MHC II determinants is regulated by CIITA isoform 1 (CIITA IF1). We found that in these cells, lipopolysaccharide stimulates the expression of MHC II genes via the activation of Erk1/2, which is mediated by Toll-like receptor 4 (TLR4). Erki/2 then phosphorylates the serine at position 357, which is located in a degron of CIITA IF 1 that leads to its monoubiquitylation. Thus modified, CIITA IF 1 binds P-TEFb, which mediates the elongation of RNA polymerise II and cotranscriptional processing of nascent transcripts. This induction leads to the expression of MHC II genes. Subsequent polyubiquitylation results in the degradation of CIITA IF 1. Thus, the signaling cascade from TLR4 to CIITA IF 1 represents one connection between innate and adaptive immunity in macrophages.
Descriptors		GENES, MHC CLASS II PROTEIN PROCESSING, POST-TRANSLATIONAL MACROPHAGES LIPOPOLYSACCHARIDES PHOSPHORYLATION TRANSCRIPTION, GENETIC POLYMERASE CHAIN REACTION ANTIBODIES, MONOCLONAL PLASMIDS CELLS, CULTURED CULTURE MEDIA