Abstract

Stat1? is a latent cytoplasmic transcription factor activated by tyrosine phosphorylation in response to IFN-(. The carboxyl terminal 38 amino acids of Stat1? are required to trigger transcription and therefore serve as a transcription activation domain (TAD). We are currently showing that the TAD of Stat1? can act as an independent transcriptional activator and that it interacts with a specific group of nuclear proteins. Mutation of serine-727 and leucine-724 in the TAD both decrease the transcriptional activation potential and the binding of the nuclear proteins. One of the bound proteins was identified as MCM5, a member of the MCM family involved in initiation of DNA replication. Both in vitro and in vivo interaction of Stat1? and MCM5 were demonstrated. Moreover the in vitro interaction required the conserved seriene-727 and was enhanced by its phosphorylation. Transient over-expression of MCM5 enhanced transcriptional activation by Stat1? in a serine 72 7-dependen t manner. Finally, changes in the level of nucle bound MCM5 during the cell cycle correlated with the changes in transcriptional response to IFN-( acting through Stat1? in a serine-727 and leucine 724-dependent manner to play a role in optimal transcriptional activation. A paper describing this work has been accepted for publication. Cont.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Biotechnology Resource Grants (P41)
Project #
5P41RR000862-26
Application #
6118310
Study Section
Project Start
1998-12-10
Project End
1999-11-30
Budget Start
1998-10-01
Budget End
1999-09-30
Support Year
26
Fiscal Year
1999
Total Cost
Indirect Cost

  Institution

Name
Rockefeller University
Department
Type
DUNS #
071037113
City
New York
State
NY
Country
United States
Zip Code
10065

  Publications

Manning, Lois R; Popowicz, Anthony M; Padovan, Julio C et al. (2017) Gel filtration of dilute human embryonic hemoglobins reveals basis for their increased oxygen binding. Anal Biochem 519:38-41
Boice, Michael; Salloum, Darin; Mourcin, Frederic et al. (2016) Loss of the HVEM Tumor Suppressor in Lymphoma and Restoration by Modified CAR-T Cells. Cell 167:405-418.e13
Chait, Brian T; Cadene, Martine; Olinares, Paul Dominic et al. (2016) Revealing Higher Order Protein Structure Using Mass Spectrometry. J Am Soc Mass Spectrom 27:952-65
Krutchinsky, Andrew N; Padovan, Júlio C; Cohen, Herbert et al. (2015) Maximizing ion transmission from atmospheric pressure into the vacuum of mass spectrometers with a novel electrospray interface. J Am Soc Mass Spectrom 26:649-58
Mast, Fred D; Rachubinski, Richard A; Aitchison, John D (2015) Signaling dynamics and peroxisomes. Curr Opin Cell Biol 35:131-6
Krutchinsky, Andrew N; Padovan, Júlio C; Cohen, Herbert et al. (2015) Optimizing electrospray interfaces using slowly diverging conical duct (ConDuct) electrodes. J Am Soc Mass Spectrom 26:659-67
Oricchio, Elisa; Papapetrou, Eirini P; Lafaille, Fabien et al. (2014) A cell engineering strategy to enhance the safety of stem cell therapies. Cell Rep 8:1677-1685
Zhong, Yu; Morris, Deanna H; Jin, Lin et al. (2014) Nrbf2 protein suppresses autophagy by modulating Atg14L protein-containing Beclin 1-Vps34 complex architecture and reducing intracellular phosphatidylinositol-3 phosphate levels. J Biol Chem 289:26021-37
Xue, John Z; Woo, Eileen M; Postow, Lisa et al. (2013) Chromatin-bound Xenopus Dppa2 shapes the nucleus by locally inhibiting microtubule assembly. Dev Cell 27:47-59
Indiani, Chiara; O'Donnell, Mike (2013) A proposal: Source of single strand DNA that elicits the SOS response. Front Biosci (Landmark Ed) 18:312-23

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