Role of the immediate early response 3 (IER3) gene in cellular stress response, inflammation and tumorigenesis.
The expression of the early response gene immediate early response 3 (IER3), formerly known as IEX-1, is induced by a great variety of stimuli, such as growth factors, cytokines, ionizing radiation, viral infection and other types of cellular stress. Being of a rather unique protein structure not sharing any similarity to other vertebrate proteins, IER3 plays a complex and to some extent contradictory role in cell cycle control and apoptosis. As outlined in this review, these effects of IER3 relate to an interference with certain signalling pathways, in particular NF-κB, MAPK/ERK and PI3K/Akt. In addition to numerous functional data relying on cell culture based studies, transgenic and knock-out mouse models revealed an involvement of IER3 expression in immune functions and in the physiology of the cardiovascular system. Deficiency of IER3 expression in mice results in an aberrant immune regulation and enhanced inflammation, in an alteration of blood pressure control and hypertension or in an impaired genomic stability. A number of patient related studies revealed an involvement of IER3 in tumorigenesis in a cell-type dependent but not yet understood manner. Future studies should establish the potential of IER3 as a new predictive marker and as a molecular target in human diseases such as cancer, inflammatory diseases or hypertension.
Department of Internal Medicine I, Laboratory of Molecular Gastroenterology & Hepatology, UKSH-Campus Kiel, Arnold-Heller-Straße 3, Bldg. 6, 24105 Kiel, Germany.
Alexander
A
Arlt
Heiner
H
Schäfer
D000818:Animals; D017209:Apoptosis / Q000235:genetics; D051017:Apoptosis Regulatory Proteins / Q000235:genetics*; D006801:Humans; D017874:Immediate-Early Proteins / Q000235:genetics*; D007249:Inflammation / Q000235:genetics; D008565:Membrane Proteins / Q000235:genetics*; D051379:Mice; D015398:Signal Transduction
D051017:Apoptosis Regulatory Proteins; C099815:IER3 protein, human; C518820:IEX-1 protein, mouse; D017874:Immediate-Early Proteins; D008565:Membrane Proteins