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EOH Events

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Event
Thu 12/5/2019 11:00AM - 12:00PM
EOH Journal Club
Protein Arginine Methyltransferase 4 (PRMT4) mediates lymphopenia in experimental sepsis EOH Journal Club
Protein Arginine Methyltransferase 4 (PRMT4) mediates lymphopenia in experimental sepsis
Thu 12/5/2019 11:00AM - 12:00PM
4140 Public Health, Young Seminar Room

Presenter: Rushikesh Deshpande

Paper: Protein Arginine Methyltransferase 4 (PRMT4) mediates lymphopenia in experimental sepsis

Authors: Yandong Lai, Xiuying Li, Tiao Li, Yan Chen, Chen Long, Toru Nyunoya, Kong Chen,Georgios D. Kitsios,Seyed Mehdi Nouraie,Yingze Zhang, Bryan J. McVerry, Janet S. Lee,Rama K. Mallampalli, and Chunbin Zou

Abstract:
Onehallmark of sepsis is a reduced number of lymphocytes, termed lymphopenia,that occurs from decreased lymphocyte proliferation or increased cell death contributing to immune suppression. Histone modification enzymes regulate immunity by epigenetically modulating chromatin architecture, however, the role of these enzymes in lymphopenia remains elusive. In this study, we identified that a chromatin modulator Protein Arginine N-methyltransferase 4/Coactivator-Associated Arginine Methyltransferase 1 (PRMT4/ CARM1) that is elevated systemically inseptic patients and experimental sepsis, and is crucialfor inducing T-lymphocyte apoptosis.An E3 ubiquitin ligase SCFFBXO9 docks on PRMT4 via a phosphodegron to ubiquitinate the protein at K228 for ubiquitin proteasomal degradation.  High PRMT4 expression resulted from reduced levels of SCFFBXO9 that led to increased lymphocyte cell death after Escherichia coliorlipopolysaccharide(LPS) exposure. Ectopic expression of PRMT4 protein caused substantially mphocytedeathvia caspase 3 mediated cell death signaling, and knockout of PRMT4 abolished LPS mediated lymphocyte cell death. PRMT4 inhibition with a small molecule compound attenuated lymphocyte death in complementary models of sepsis. These findings demonstrate a previously uncharacterized role of a key chromatin modulator in lymphocytesurvival that may shed light on devising unique therapeutic modalities to lessen severity of septic immunosuppression.


4140 Public Health, Young Seminar Room
Fri 12/6/2019 1:00PM - 2:00PM
EOH Seminar Series
Role of Oxidative DNA damage in telomere maintenance: Implications for Aging and Cancer EOH Seminar Series
Role of Oxidative DNA damage in telomere maintenance: Implications for Aging and Cancer
Fri 12/6/2019 1:00PM - 2:00PM
A719 Public Health


A719 Public Health

Recent Events

EOH Seminar Series

IL-33 Regulation in Allergic Disease - Marsha Wills-Karp - Johns Hopkins Bloomberg Sch of Pub Health

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Friday 11/9 1:00PM - 2:00PM
A719 Public Health
Marsha Wills-Karp
Anna M. Baetjer Professor of Environmental Health
Chair, Department of Environmental Health and Engineering
Johns Hopkins Bloomberg School of Public Health
Whiting School of Engineering
Baltimore, MD

IL-33 Regulation in Allergic Disease
Enrolled Users:

Last Updated On Wednesday, October 24, 2018 by Johnston, Cindy S
Created On Wednesday, October 24, 2018

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