IRT-1, a novel interferon-gamma-responsive transcript encoding a growth-suppressing basic leucine zipper protein.
Interferon-gamma (IFN-gamma) inhibits proliferation of vascular smooth muscle cells (VSMCs) in culture and reduces arterial restenosis post-balloon angioplasty. The identification and characterization of IFN-gamma-specific transcripts in VSMCs are an important approach to discern the molecular mechanisms underlying vascular proliferative disease. In this report, we describe IRT-1, a novel mRNA transcript constitutively expressed in a number of human tissues, but expressed in human VSMCs only when they are stimulated with IFN-gamma. This mRNA expression is induced >200-fold 72 h after IFN-gamma treatment. IRT-1 mRNA is also acutely expressed in rat carotid arteries that are injured by balloon angioplasty. The IRT-1 cDNA transcript encodes a basic protein that contains a leucine zipper motif, a core nuclear localization sequence, and a single strongly hydrophobic region. Constitutive IRT-1 mRNA expression in human peripheral blood lymphocytes is reduced when these cells are stimulated to proliferate. Overexpression of IRT-1 protein in VSMCs alters their morphology and dramatically reduces their proliferative capacity. This study suggests that IRT-1 is an IFN-gamma-inducible factor that may regulate the progression of vascular proliferative diseases.
Autieri
M V
MV
Department of Molecular Biology, Deborah Heart and Lung Research Institute, Browns Mills, New Jersey 08015, USA.
Agrawal
N
N
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002135:Calcium-Binding Proteins; D002455:Cell Division / Q000235:genetics; D002478:Cells, Cultured; D003001:Cloning, Molecular; D003513:Cycloheximide / Q000494:pharmacology; D004268:DNA-Binding Proteins / Q000737:chemistry*; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007150:Immunohistochemistry; D007371:Interferon-gamma / Q000494:pharmacology*; D016350:Leucine Zippers / Q000235:genetics*; D008214:Lymphocytes / Q000502:physiology; D008297:Male; D008840:Microfilament Proteins; D008969:Molecular Sequence Data; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017422:Sequence Analysis, DNA; D014158:Transcription, Genetic / Q000235:genetics
C112986:AIF1 protein, human; D002135:Calcium-Binding Proteins; D004268:DNA-Binding Proteins; D008840:Microfilament Proteins; D012333:RNA, Messenger; D007371:Interferon-gamma; D003513:Cycloheximide