1: Blood. 2003 Apr 15;101(8):3058-64. Epub 2002 Dec 12. 

Regulation of human beta 2-microglobulin transactivation in hematopoietic cells.

Gobin SJ, Biesta P, Van den Elsen PJ.

Department of Immunohematology and Blood Transfusion, Leiden University Medical
Center, Leiden, The Netherlands.

beta(2)-Microglobulin (beta(2)m) is a chaperone of major histocompatibility
complex (MHC) class I (-like) molecules that play a central role in antigen
presentation, immunoglobulin transport, and iron metabolism. It is therefore of
importance that beta(2)m is adequately expressed in cells that perform these
functions, such as hematopoietic cells. In this study, we investigated the
transcriptional regulation of beta(2)m in lymphoid and myeloid cell lines
through a promoter containing a putative E box, Ets/interferon-stimulated
response element (ISRE), and kappa B site. Here we show that upstream
stimulatory factor 1 (USF1) and USF2 bind to the E box and regulate beta(2)m
transactivation. The nuclear factor kappa B (NF-kappa B) subunits p50 and p65
bind to the kappa B box and p65 transactivates beta(2)m. Interferon regulatory
factor 1 (IRF1), IRF2, IRF4, and IRF8, but not PU.1, bind to the Ets/ISRE, and
IRF1 and IRF3 are strong transactivators of beta(2)m. Together, all 3 boxes are
important for the constitutive and cytokine-induced levels of beta(2)m
expression in lymphoid and myeloid cell types. As such, beta(2)m transactivation
is under the control of important transcriptional pathways, which are activated
during injury, infection, and inflammation.

PMID: 12480693 [PubMed - indexed for MEDLINE]


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