These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: Y-box-binding protein YB-1 mediates transcriptional repression of human alpha 2(I) collagen gene expression by interferon-gamma.
    Author: Higashi K, Inagaki Y, Suzuki N, Mitsui S, Mauviel A, Kaneko H, Nakatsuka I.
    Journal: J Biol Chem; 2003 Feb 14; 278(7):5156-62. PubMed ID: 12446674.
    Abstract:
    We have demonstrated previously that a proximal element within the human alpha2(I) collagen gene (COL1A2) promoter mediates transcriptional repression by interferon-gamma (IFN-gamma), and designated this region the IFN-gamma response element (IgRE). Screening of a human fibroblast cDNA expression library with a radiolabeled IgRE probe exclusively yielded clones with a sequence identical to that of the transcription factor YB-1. Electrophoretic mobility shift assays (EMSA) using various IgRE-derived oligonucleotide probes containing serial two-base mutations showed that YB-1 protein was preferentially bound to the pyrimidine-rich sequence within the IgRE. This region is located immediately downstream of and partly overlaps the previously reported Sp1/Sp3 binding site. Overexpression of YB-1 in human dermal fibroblasts decreased steady state levels of COL1A2 mRNA and repressed COL1A2 promoter activity in a dose-dependent manner. This inhibitory effect of YB-1 on COL1A2 expression was abolished by mutations of the IgRE shown to prevent YB-1 binding in EMSA. In addition, these mutations also abolished the inhibitory effect of IFN-gamma, suggesting that YB-1 mediates the inhibitory action of IFN-gamma on COL1A2 promoter through its binding to the IgRE. Also, overexpression of a deletion mutant YB-1, which lacks the carboxyl-terminal domain, abrogated the repression of COL1A2 transcription by IFN-gamma. A functional correlation between IFN-gamma and YB-1 was further supported by luciferase assays using four tandem repeats of the Y-box consensus oligonucleotide linked to a minimal promoter. EMSA and Western blot analysis using cytoplasmic and nuclear proteins implied that IFN-gamma promotes the nuclear translocation of YB-1. Direct evidence for the nuclear translocation of YB-1 by IFN-gamma was further provided by using a YB-1-green fluorescent protein expression plasmid transfected into human fibroblasts. Altogether, this study represents the definitive identification of the transcription factor responsible for IFN-gamma-elicited inhibition of COL1A2 expression, namely YB-1.
    [Abstract] [Full Text] [Related] [New Search]