Author/Editor		Drozina, Gorazd; Kohoutek, Jiri; Nishiya, Tadashi; Peterlin, Matija B
Title		Sequential modifications in class II transactivator isoform 1 induced by lipopolysaccharide stimulate major histocompatibility complex class II transcription in macrophages
Type		članek
Source		J Biol Chem
Vol. and No.		Letnik 281, št. 52
Publication year		2006
Volume		str. 39963-70
Language		eng
Abstract		By presenting antigenic peptides on major histocompatibility complex class (MHC) II determinants to CD4(+) T cells, macrophages help to direct the establishment of adaptive immunity. 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. Erk1/2 then phosphorylates the serine at position 357, which is located in a degron of CIITA isoform 1 that leads to its monoubiquitylation. Thus modified, CIITA isoform 1 binds P-TEFb, which mediates the elongation of RNA polymerase II and co-transcriptional processing of nascent transcripts. This induction leads to the expression of MHC II genes. Subsequent polyubiquitylation results in the degradation of CIITA isoform 1. Thus, the signaling cascade from Toll-like receptor 4 to CIITA isoform 1 represents one connection between innate and adaptive immunity in macrophages.
Descriptors		TRANSCRIPTION, GENETIC ANIMALS COS CELLS CELL LINE CERCOPITHECUS AETHIOPS HELA CELLS HISTOCOMPATIBILITY ANTIGENS CLASS II LIPOPOLYSACCHARIDES MACROPHAGES MICE MICE, INBRED C57BL MICE, KNOCKOUT NUCLEAR PROTEINS RABBITS TRANS-ACTIVATORS