Abstract

The proposed research aims to study the role of putative cell death genes [encoding interleukin-1 beta converting enzyme (ICE), mICE2, and Nedd-2] in normal mouse development and in tumorigenesis. The importance of these genes derives from the fact that they have homology to the C. elegans cell death gene ced-3.The proposed experiments test whether these genes function similarly to ced-3 in mammalian cells. Specifically, Dr. Yuan will 1) isolate genomic clones and construct gene-targeting vector to disrupt gene activity, 2) establish ES cell cultures and transgenic mice with these disrupted genes, 3) characterize the developmental phenotypes of these transgenic mice, 4) determine if the mutations are tumorigenic in the animals, and 5) study tumorigenesis in cell lines derived from the mouse strains.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Project (R01)
Project #
1R01AG012859-01
Application #
2054668
Study Section
Molecular Cytology Study Section (CTY)
Project Start
1994-09-01
Project End
1997-08-31
Budget Start
1994-09-01
Budget End
1995-08-31
Support Year
1
Fiscal Year
1994
Total Cost
Indirect Cost

  Institution

Name
Massachusetts General Hospital
Department
Type
DUNS #
City
Boston
State
MA
Country
United States
Zip Code
02199

  Publications

Vakifahmetoglu-Norberg, Helin; Xia, Hong-guang; Yuan, Junying (2015) Pharmacologic agents targeting autophagy. J Clin Invest 125:5-13
Xiao, Juan; Zhang, Tao; Xu, Daichao et al. (2015) FBXL20-mediated Vps34 ubiquitination as a p53 controlled checkpoint in regulating autophagy and receptor degradation. Genes Dev 29:184-96
Zhang, Tao; Dong, Kangyun; Liang, Wei et al. (2015) G-protein-coupled receptors regulate autophagy by ZBTB16-mediated ubiquitination and proteasomal degradation of Atg14L. Elife 4:e06734
Xu, Daichao; Zhang, Tao; Xiao, Juan et al. (2015) Modification of BECN1 by ISG15 plays a crucial role in autophagy regulation by type I IFN/interferon. Autophagy 11:617-28
Zhou, Wen; Yuan, Junying (2014) Necroptosis in health and diseases. Semin Cell Dev Biol 35:14-23
Ofengeim, Dimitry; Yuan, Junying (2013) Regulation of RIP1 kinase signalling at the crossroads of inflammation and cell death. Nat Rev Mol Cell Biol 14:727-36
Hitomi, Junichi; Christofferson, Dana E; Ng, Aylwin et al. (2008) Identification of a molecular signaling network that regulates a cellular necrotic cell death pathway. Cell 135:1311-23
Boyce, M; Py, B F; Ryazanov, A G et al. (2008) A pharmacoproteomic approach implicates eukaryotic elongation factor 2 kinase in ER stress-induced cell death. Cell Death Differ 15:589-99
Boyce, M; Yuan, J (2006) Cellular response to endoplasmic reticulum stress: a matter of life or death. Cell Death Differ 13:363-73
Kang, S J; Wang, S; Kuida, K et al. (2002) Distinct downstream pathways of caspase-11 in regulating apoptosis and cytokine maturation during septic shock response. Cell Death Differ 9:1115-25

Showing the most recent 10 out of 16 publications