PMID- 10586057
OWN - NLM
STAT- MEDLINE
DCOM- 20000106
LR  - 20161124
IS  - 0022-1767 (Print)
IS  - 0022-1767 (Linking)
VI  - 163
IP  - 12
DP  - 1999 Dec 15
TI  - Analysis of the defect in IFN-gamma induction of MHC class II genes in G1B cells:
      identification of a novel and functionally critical leucine-rich motif
      (62-LYLYLQL-68) in the regulatory factor X 5 transcription factor.
PG  - 6622-30
AB  - MHC class II deficiency found in bare lymphocyte syndrome patients results from
      the absence or dysfunction of MHC class II transcriptional regulators, such as
      regulatory factor X (RFX) and class II transactivator (CIITA). Understanding the 
      roles of these factors has been greatly facilitated by the study of genetic
      defects in cell lines of bare lymphocyte syndrome patients, as well as in cell
      lines that have been generated by chemical mutagenesis in vitro. The latter group
      includes MHC class II-deficient lines that are no longer responsive to induction 
      by IFN-gamma. Here, we show that the defect in G1B, one such cell line, is
      attributed to the lack of functional RFX5, the largest subunit of RFX. The RFX5
      gene isolated from G1B cells contains two separate single-base pair mutations.
      One alteration does not exhibit a phenotype, whereas a leucine-to-histidine
      mutation eliminates DNA-binding and transactivating functions. This mutation lies
      outside of previously defined functional domains of RFX5 but within an unusual,
      leucine-rich region (62-LYLYLQL-68). To further investigate the significance of
      the leucine-rich region, we targeted all neighboring leucine residues for
      mutagenesis. These mutants were also unable to transactivate a MHC class II
      reporter gene, confirming that these leucine residues play an essential role in
      RFX activity and characterize a novel leucine-rich motif.
FAU - Brickey, W J
AU  - Brickey WJ
AD  - UNC Lineberger Comprehensive Cancer Center, Department of Immunology and
      Microbiology, School of Dentistry, University of North Carolina, Chapel Hill
      27599, USA.
FAU - Wright, K L
AU  - Wright KL
FAU - Zhu, X S
AU  - Zhu XS
FAU - Ting, J P
AU  - Ting JP
LA  - eng
GR  - AI29564/AI/NIAID NIH HHS/United States
GR  - AI41580/AI/NIAID NIH HHS/United States
GR  - CA09156/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Immunol
JT  - Journal of immunology (Baltimore, Md. : 1950)
JID - 2985117R
RN  - 0 (DNA, Neoplasm)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (HLA-DR Antigens)
RN  - 0 (HLA-DR alpha-Chains)
RN  - 0 (Neoplasm Proteins)
RN  - 0 (Nuclear Proteins)
RN  - 0 (RFX5 protein, human)
RN  - 0 (Regulatory Factor X Transcription Factors)
RN  - 0 (Transcription Factors)
RN  - 82115-62-6 (Interferon-gamma)
RN  - GMW67QNF9C (Leucine)
RN  - K848JZ4886 (Cysteine)
SB  - IM
MH  - Amino Acid Motifs/immunology
MH  - Amino Acid Sequence
MH  - Base Pairing/genetics
MH  - Base Sequence
MH  - Cloning, Molecular
MH  - Cysteine/genetics/metabolism
MH  - DNA, Neoplasm/metabolism
MH  - DNA-Binding Proteins/biosynthesis/genetics/isolation & purification/*metabolism
MH  - Gene Expression Regulation, Neoplastic/*immunology
MH  - Genes, MHC Class II/*immunology
MH  - Genetic Complementation Test
MH  - HLA-DR Antigens/biosynthesis/metabolism
MH  - HLA-DR alpha-Chains
MH  - Humans
MH  - Interferon-gamma/*physiology
MH  - Leucine/genetics/*metabolism
MH  - Molecular Sequence Data
MH  - Neoplasm Proteins/metabolism
MH  - Nuclear Proteins/isolation & purification/metabolism
MH  - Phenotype
MH  - Point Mutation
MH  - Protein Structure, Tertiary
MH  - Regulatory Factor X Transcription Factors
MH  - Transcription Factors/biosynthesis/genetics/isolation & purification/*metabolism
MH  - Transcriptional Activation/genetics
MH  - Tumor Cells, Cultured
EDAT- 1999/12/10 00:00
MHDA- 1999/12/10 00:01
CRDT- 1999/12/10 00:00
PHST- 1999/12/10 00:00 [pubmed]
PHST- 1999/12/10 00:01 [medline]
PHST- 1999/12/10 00:00 [entrez]
AID - ji_v163n12p6622 [pii]
PST - ppublish
SO  - J Immunol. 1999 Dec 15;163(12):6622-30.