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STAT activation and differential complex formation dictate selectivity of interferon responses

100%

Wesoly J., Szweykowska-Kulinska Z., Bluyssen H. A. R.

Acta Biochimica Polonica

2007

tom 54

nr 1

Interferons (IFNs) induce gene expression by phosphorylating latent transcription factors belonging to the signal transducer and activator of transcription (STAT) family, mediated by janus kinases (Jaks). STAT dimers directly activate genes containing the IFNγ activation site (GAS) DNA element, with different STAT proteins displaying slightly different intrinsic DNA binding specificities. The combinatorial association of STATs with the additional DNA binding adaptor protein interferon regulatory factor (IRF)9 expands the range of enhancer elements that can be targeted by the JAK-STAT pathway to interferon-stimulated response element (ISRE) and IRF response element (IRE). Based on the amino-acid sequence similarity within the IRF family and functional overlap with the STAT family, in this paper we hypothesize that other IRF members could serve as adapter proteins for the STATs during IFN responses to redirect them to subsets of ISRE, GAS and/or IRE-containing IFN-stimulated genes (ISGs). In addition, the fact that STAT2 homodimers are not capable of binding consensus GAS sites leaves the possibility for a novel type of DNA-binding site bound by STAT2 homodimers and potentially other STAT complexes.

DNA constructs designed to produce short hairpin, interfering RNAs in transgenic mice sometimes show early lethality and an interferon response

80%

Cao W., Hunter R., Strnatka D., McQueen C. A., Erickson R. P.

Journal of Applied Genetics

2005

tom 46

nr 2

Arylamine N-acetyltransferase (NAT) genes were targeted for inhibition using short hairpin RNA (shRNA) using two different RNA polymerase III promoters. Constructs were developed for NAT1 and NAT2, the endogenous mouse genes, and for human NAT1. There were fetal and neonatal deaths with these constructs, perhaps due in part to an interferon response as reflected in increases in oligoadenylate synthetase I mRNA levels. Seven out of 8 founders with the U6 promoter generated offspring but only 2 gave positive offspring. Out of 15 founders for H1 promoted constructs, only 4 had positive offspring. When transgenic lines were successfully established, the expression of the targeted genes was variable between animals and was not generally inhibitory.

Ograniczanie wyników

1 Acta Biochimica Polonica

1 Journal of Applied Genetics

1 Bluyssen H. A. R.

1 Cao W.

1 Erickson R. P.

1 Hunter R.

1 McQueen C. A.

1 Strnatka D.

1 Szweykowska-Kulinska Z.

1 Wesoly J.

1 2007

1 2005

Wyniki wyszukiwania

STAT activation and differential complex formation dictate selectivity of interferon responses

DNA constructs designed to produce short hairpin, interfering RNAs in transgenic mice sometimes show early lethality and an interferon response