Author/Editor		Klampfer, Lidija; Huang, Jie; Augenlicht, Leonard
Title		STAT1 dependent and STAT1 independent signalling by IFN-gamma
Translated title		Od STAT1 odvisen in STAT1 neodvisen prenos signala, ki ga posreduje IFN-gama
Type		članek
Source		Med Razgl
Vol. and No.		Letnik 43, št. Suppl 5
Publication year		2004
Volume		str. 37-42
Language		eng
Abstract		Interferon gamma (IFN-gamma) has a crucial role in regulating the anti-viral response, cell proliferation, apoptosis, immune surveillance and tumor suppression. It exerts its biological activity through altering gene expression, most notably through activation of the latent transcription factors, signal transducer and activator of transcription 1 (STAT1) and STAT2. Although the expression of the majority of IFN gamma target genes requires STAT1, we and others have demonstrated that IFN regulates the expression of a subset of its target genes through pathways that bypass STAT1. We demonstrated that histone deacetylase (HDAC) activity is required for signaling by STAT1 and that inhibitors of HDAC activity interfere with the expression of IFN gamma target genes that depend on STAT1, such as IRF-1 and IRF-9. In contrast, we demonstrated that HDAC inhibitors did not preclude the expression of a subset of IFN-gamma target genes, such as STAT1, STAT2 and caspase-7. Finally, we established that silencing of STAT1 expression through small interfering RNA does not impair the basal or IFN-gamma induced expression of STAT2 and caspase-7, confirming that the expression of these genes occurs in a STAT1 independent manner.
Summary		Interferon gama (IFN-gama) ima pomembno vlogo pri celičnem razmnoževanju, apoptozi, imunskem odzivu, obrambi pred virusi in tumorji. Svojo biološko vlogo posreduje s spodbujanjem različnih genov. Pri tem uporablja latentna transkripcijska faktorja STAT1 in STAT2. STAT1 in STAT2 sta potrebna za aktivacijo večine na IFN odzivnih genov. Skupaj z drugimi smo pokazali, da lahko IFN uravnava določeno skupino genov tako, da se izogne aktivaciji STAT1. Za takšno uravnavanje je potrebna aktivnost histonske deacetilaze (HDAC). Zaviralci HDAC preprečijo aktivacijo od IFN odvisnih genov IRF-1 in IRF-9, ki za svoje izražanje potrebujejo aktivacijo s STAT1. V naslednjih poskusih smo ugotovili, da zaviralci HDAC ne preprečijo izražanja od IFN odvisnih genov STAT1, STAT2 in kaspaze 7. Na koncu smo še ugotovili, da prekinitev dejavnosti STAT1 z majhnimi interferirajočimi odlomki RNA ne prepreči izražanja STAT2 in kaspaze 7, kar je dokaz, da je aktivacija teh genov neodvisna od aktivacije s STAT1.
Descriptors		INTERFERON TYPE II SIGNAL TRANSDUCTION TRANSCRIPTION FACTORS