Abstract

The overall goal of this research program is to understand the mechanism of signal transduction mediated by MAP kinases in mammalian cells. A focus of this study is the c-Jun NH2-terminal kinase (JNK) group of MAP kinases. Many of the components of the JNK protein kinase cascade have been identified by molecular cloning and have been characterized in biochemical studies. However, a complete understanding of the physiological function of JNK has remained elusive. The long-term goal of this research is to define the molecular mechanisms and physiological significance of JNK activation caused by inflammatory cytokines. Achievement of the goals of this proposal will increase understanding of the molecular mechanism of MAP kinase signal transduction in vivo. This information represents a basis for the design of novel therapeutic strategies for the treatment of proliferative diseases, including cancer.
The Specific Aims of thisproposal are to examine: 1. The physiological role of JNK in TNF signal transduction. 2. The mechanism of JNK-induced apoptosis.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA065861-13
Application #
7350186
Study Section
Cellular Signaling and Dynamics Study Section (CSD)
Program Officer
Mccarthy, Susan A
Project Start
1995-07-01
Project End
2010-12-31
Budget Start
2008-01-01
Budget End
2008-12-31
Support Year
13
Fiscal Year
2008
Total Cost
$278,337
Indirect Cost

  Institution

Name
University of Massachusetts Medical School Worcester
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
603847393
City
Worcester
State
MA
Country
United States
Zip Code
01655

  Publications

Lu, Huimin; Wang, Tao; Li, Jing et al. (2016) ?v?6 Integrin Promotes Castrate-Resistant Prostate Cancer through JNK1-Mediated Activation of Androgen Receptor. Cancer Res 76:5163-74
Han, Myoung Sook; Jung, Dae Young; Morel, Caroline et al. (2013) JNK expression by macrophages promotes obesity-induced insulin resistance and inflammation. Science 339:218-22
Goel, Hira Lal; Sayeed, Aejaz; Breen, Michael et al. (2013) ?1 integrins mediate resistance to ionizing radiation in vivo by inhibiting c-Jun amino terminal kinase 1. J Cell Physiol 228:1601-9
Hübner, Anette; Mulholland, David J; Standen, Claire L et al. (2012) JNK and PTEN cooperatively control the development of invasive adenocarcinoma of the prostate. Proc Natl Acad Sci U S A 109:12046-51
Cellurale, Cristina; Girnius, Nomeda; Jiang, Feng et al. (2012) Role of JNK in mammary gland development and breast cancer. Cancer Res 72:472-81
Das, Madhumita; Garlick, David S; Greiner, Dale L et al. (2011) The role of JNK in the development of hepatocellular carcinoma. Genes Dev 25:634-45
Cellurale, Cristina; Sabio, Guadalupe; Kennedy, Norman J et al. (2011) Requirement of c-Jun NH(2)-terminal kinase for Ras-initiated tumor formation. Mol Cell Biol 31:1565-76
Liu, Wei; Zi, Min; Chi, Hongbo et al. (2011) Deprivation of MKK7 in cardiomyocytes provokes heart failure in mice when exposed to pressure overload. J Mol Cell Cardiol 50:702-11
Zou, Weiguo; Greenblatt, Matthew B; Shim, Jae-Hyuck et al. (2011) MLK3 regulates bone development downstream of the faciogenital dysplasia protein FGD1 in mice. J Clin Invest 121:4383-92
Kant, Shashi; Swat, Wojciech; Zhang, Sheng et al. (2011) TNF-stimulated MAP kinase activation mediated by a Rho family GTPase signaling pathway. Genes Dev 25:2069-78

Showing the most recent 10 out of 65 publications