Abstract

The overall goal of this project is to understand the mechanisms of transcriptional signaling by double-stranded RNA. the expression of several interferon-inducible genes is directly induced by double-stranded RNA. We will investigate how double-stranded RNA regulates the transcription of genes. For this purpose, the cis-acting sequences required for the effects of double-stranded RNA will be identified and the cognate trans-acting factors which mediate this induction will be analyzed. Another aim of the project is to identify cellular proteins which specifically bind double-stranded RNA. These proteins will be purified, their cDNA clones will be isolated, and their putative roles is transcriptional signaling by double-stranded RNA will be evaluated. the proposed studies will provide a better understanding of the regulation of expression of double-stranded RNA-inducible genes which encode many important regulatory proteins such as interferons, interleukins, and cell adhesion molecules. Our studies also reveal the nature of overlap between the signal transduction pathways used by interferons and double-stranded RNA for inducing transcription of the same genes.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Program Projects (P01)
Project #
5P01CA062220-05
Application #
6269634
Study Section
Project Start
1998-06-01
Project End
1999-05-31
Budget Start
1997-10-01
Budget End
1998-09-30
Support Year
5
Fiscal Year
1998
Total Cost
Indirect Cost

  Institution

Name
Cleveland Clinic Lerner
Department
Type
DUNS #
017730458
City
Cleveland
State
OH
Country
United States
Zip Code
44195

  Publications

Sarvestani, Samaneh K; Signs, Steven A; Lefebvre, Veronique et al. (2018) Cancer-predicting transcriptomic and epigenetic signatures revealed for ulcerative colitis in patient-derived epithelial organoids. Oncotarget 9:28717-28730
Cai, Gang; Zhu, Liang; Chen, Xing et al. (2018) TRAF4 binds to the juxtamembrane region of EGFR directly and promotes kinase activation. Proc Natl Acad Sci U S A 115:11531-11536
Herjan, Tomasz; Hong, Lingzi; Bubenik, Jodi et al. (2018) IL-17-receptor-associated adaptor Act1 directly stabilizes mRNAs to mediate IL-17 inflammatory signaling. Nat Immunol 19:354-365
Veleeparambil, Manoj; Poddar, Darshana; Abdulkhalek, Samar et al. (2018) Constitutively Bound EGFR-Mediated Tyrosine Phosphorylation of TLR9 Is Required for Its Ability To Signal. J Immunol 200:2809-2818
Nan, Jing; Wang, Yuxin; Yang, Jinbo et al. (2018) IRF9 and unphosphorylated STAT2 cooperate with NF-?B to drive IL6 expression. Proc Natl Acad Sci U S A 115:3906-3911
Zhou, Hao; Bulek, Katarzyna; Li, Xiao et al. (2017) IRAK2 directs stimulus-dependent nuclear export of inflammatory mRNAs. Elife 6:
Wang, Chenhui; Zhang, Cun-Jin; Martin, Bradley N et al. (2017) IL-17 induced NOTCH1 activation in oligodendrocyte progenitor cells enhances proliferation and inflammatory gene expression. Nat Commun 8:15508
Wang, Yuxin; Nan, Jing; Willard, Belinda et al. (2017) Negative regulation of type I IFN signaling by phosphorylation of STAT2 on T387. EMBO J 36:202-212
Doherty, Mary R; Cheon, HyeonJoo; Junk, Damian J et al. (2017) Interferon-beta represses cancer stem cell properties in triple-negative breast cancer. Proc Natl Acad Sci U S A 114:13792-13797
Liu, Caini; Zhu, Liang; Fukuda, Koichi et al. (2017) The flavonoid cyanidin blocks binding of the cytokine interleukin-17A to the IL-17RA subunit to alleviate inflammation in vivo. Sci Signal 10:

Showing the most recent 10 out of 253 publications