): The tumor necrosis factor family of cytokines induces a wide number of biological effects that directly influence cell growth, cell differentiation, and apoptosis. A common feature of this family is the existence of transmembrane receptors with multiple conserved cysteine-rich motifs in the ligand binding domain and a short cytoplasmic domain. The TNF receptor superfamily includes the Fas antigen, two TNF receptors, CD40, CD30, and the p 75 neurotrophin receptor. Several of these receptors contain a death domain sequence which is responsible for transmitting cell death signals. These receptors contain a death domain sequence which is responsible for transmitting cell death signals. These receptors can recruit and bind adapter molecules, which in turn associate with cytoplasmic proteins associated with caspase activation and serine/threonine protein kinases activities. In this renewal application, we will focus on an adapter molecule, SC-1, a novel zinc finger protein which belongs to a family of genes implicated in tumor progression. SC-1 was first identified as a p75 receptor binding protein; subsequent studies indicate that it is associated with growth arrest events. The further characterization of this zinc finger protein with the actions of TNF receptor members will likely yield additional mechanisms concerning cell proliferation. These studies will provide insight into mechanisms responsible for cytokine actions during inflammation, injury and disease states.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA056490-11
Application #
6624662
Study Section
Metabolic Pathology Study Section (MEP)
Program Officer
Mufson, R Allan
Project Start
1992-04-10
Project End
2004-11-30
Budget Start
2003-01-09
Budget End
2004-11-30
Support Year
11
Fiscal Year
2003
Total Cost
$277,752
Indirect Cost
Name
New York University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
121911077
City
New York
State
NY
Country
United States
Zip Code
10016
Arevalo, Juan Carlos; Pereira, Daniela B; Yano, Hiroko et al. (2006) Identification of a switch in neurotrophin signaling by selective tyrosine phosphorylation. J Biol Chem 281:1001-7
Zampieri, Niccolo; Xu, Chong-Feng; Neubert, Thomas A et al. (2005) Cleavage of p75 neurotrophin receptor by alpha-secretase and gamma-secretase requires specific receptor domains. J Biol Chem 280:14563-71
Chittka, Alexandra; Arevalo, Juan Carlos; Rodriguez-Guzman, Maria et al. (2004) The p75NTR-interacting protein SC1 inhibits cell cycle progression by transcriptional repression of cyclin E. J Cell Biol 164:985-96
Murray, Simon S; Perez, Pilar; Lee, Ramee et al. (2004) A novel p75 neurotrophin receptor-related protein, NRH2, regulates nerve growth factor binding to the TrkA receptor. J Neurosci 24:2742-9
Jung, Kwang-Mook; Tan, Serena; Landman, Natalie et al. (2003) Regulated intramembrane proteolysis of the p75 neurotrophin receptor modulates its association with the TrkA receptor. J Biol Chem 278:42161-9
Kim, Albert H; Sasaki, Takehiko; Chao, Moses V (2003) JNK-interacting protein 1 promotes Akt1 activation. J Biol Chem 278:29830-6
Kim, Albert H; Yano, Hiroko; Cho, Han et al. (2002) Akt1 regulates a JNK scaffold during excitotoxic apoptosis. Neuron 35:697-709
Khursigara, G; Bertin, J; Yano, H et al. (2001) A prosurvival function for the p75 receptor death domain mediated via the caspase recruitment domain receptor-interacting protein 2. J Neurosci 21:5854-63
Dowling, P; Ming, X; Raval, S et al. (1999) Up-regulated p75NTR neurotrophin receptor on glial cells in MS plaques. Neurology 53:1676-82
Orlinick, J R; Vaishnaw, A; Elkon, K B et al. (1997) Requirement of cysteine-rich repeats of the Fas receptor for binding by the Fas ligand. J Biol Chem 272:28889-94

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