Sequential modifications in class II transactivator isoform 1 induced by lipopolysaccharide stimulate major histocompatibility complex class II transcription in macrophages

DROZINA, Gorazd, Jiří KOHOUTEK, Tadashi NISHIYA and B Matija PETERLIN. Sequential modifications in class II transactivator isoform 1 induced by lipopolysaccharide stimulate major histocompatibility complex class II transcription in macrophages. Journal of Biological Chemistry. Bethesda, USA: Amer. Soc. Biochem. Mol. Biol., 2006, vol. 281, No 52, p. 39963-39970. ISSN 0021-9258. Available from: https://dx.doi.org/10.1074/jbc.M608538200.

Basic information

• Original name: Sequential modifications in class II transactivator isoform 1 induced by lipopolysaccharide stimulate major histocompatibility complex class II transcription in macrophages
• Authors: DROZINA, Gorazd, Jiří KOHOUTEK, Tadashi NISHIYA and B Matija PETERLIN.
• Edition: Journal of Biological Chemistry, Bethesda, USA, Amer. Soc. Biochem. Mol. Biol. 2006, 0021-9258.

Other information

• Original language: English
• Type of outcome: Article in a journal
• Field of Study: Genetics and molecular biology
• Country of publisher: United States of America
• Confidentiality degree: is not subject to a state or trade secret
• WWW: URL
• Impact factor: Impact factor: 5.808
• Organization unit: Central European Institute of Technology
• Doi: http://dx.doi.org/10.1074/jbc.M608538200
• UT WoS: 000243033900024
• Keywords in English: ELONGATION-FACTOR-B; UBIQUITIN-MEDIATED PROTEOLYSIS; HUMAN-IMMUNODEFICIENCY-VIRUS; CREB BINDING-PROTEIN; TOLL-LIKE RECEPTORS; ACTIVATE TRANSCRIPTION; DIFFERENTIAL USAGE; DENDRITIC CELLS; CIITA FUNCTION; IFN-GAMMA
• Tags: ok
• Tags: International impact, Reviewed

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.