Abstract

(taken directly from the application): The E2A proteins, E12, and E47 (E2- 5), are members of the basic-Helix-Loop-Helix (bHLH) family of DNA binding proteins. Encoded by the E2A gene, they are ubiquitously expressed, but have also been shown to be mediate B cell-specific transcriptional activation by the immunoglobulin heavy chain enhancer. Moreover, evidence from E2A-deficient mice indicates that the proteins are absolutely necessary for the generation and/or maintenance of B cells. E47 is inactivated in a variety of non-B cells by mechanisms that include the phosphorylation of serines adjacent to the bHLH domain. This proposal aims to study the consequences of constitutively expressing E2A proteins. The question being addressed is: To what extent are the E2A proteins sufficient for B cell determination? In particular, the effects of constitutively-expressed E2A proteins will be examined in a) transiently-transfected non-B cell lines, b) stably-transformed B X T hybrid cells, and c) transgenic mice that express the proteins in targeted cell types including B and T lymphocytes. We will also identify novel E2A protein-induced genes.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Program Projects (P01)
Project #
5P01DK052558-05
Application #
6574774
Study Section
Project Start
2002-03-01
Project End
2003-02-28
Budget Start
1997-10-01
Budget End
1998-09-30
Support Year
5
Fiscal Year
2002
Total Cost
$348,824
Indirect Cost

  Institution

Name
University of Pennsylvania
Department
Type
DUNS #
042250712
City
Philadelphia
State
PA
Country
United States
Zip Code
19104

  Publications

Grant, Maria B; Caballero, Sergio; Brown, Gary A J et al. (2003) The contribution of adult hematopoietic stem cells to retinal neovascularization. Adv Exp Med Biol 522:37-45
Zhao, Fang; McCarrick-Walmsley, Ruth; Akerblad, Peter et al. (2003) Inhibition of p300/CBP by early B-cell factor. Mol Cell Biol 23:3837-46
Ptasznik, Andrzej; Urbanowska, Elzbieta; Chinta, Suneetha et al. (2002) Crosstalk between BCR/ABL oncoprotein and CXCR4 signaling through a Src family kinase in human leukemia cells. J Exp Med 196:667-78
Grant, Maria B; May, W Stratford; Caballero, Sergio et al. (2002) Adult hematopoietic stem cells provide functional hemangioblast activity during retinal neovascularization. Nat Med 8:607-12
Taichman, R; Reilly, M; Verma, R et al. (2001) Hepatocyte growth factor is secreted by osteoblasts and cooperatively permits the survival of haematopoietic progenitors. Br J Haematol 112:438-48
Zhao, F; Vilardi, A; Neely, R J et al. (2001) Promotion of cell cycle progression by basic helix-loop-helix E2A. Mol Cell Biol 21:6346-57
Guerriero, A; Langmuir, P B; Spain, L M et al. (2000) PU.1 is required for myeloid-derived but not lymphoid-derived dendritic cells. Blood 95:879-85
Majka, M; Ratajczak, J; Machalinski, B et al. (2000) Expression, regulation and function of AC133, a putative cell surface marker of primitive human haematopoietic cells. Folia Histochem Cytobiol 38:53-63
Majka, M; Ratajczak, J; Lee, B et al. (2000) The role of HIV-related chemokine receptors and chemokines in human erythropoiesis in vitro. Stem Cells 18:128-38
Lee, B; Ratajczak, J; Doms, R W et al. (1999) Coreceptor/chemokine receptor expression on human hematopoietic cells: biological implications for human immunodeficiency virus-type 1 infection. Blood 93:1145-56

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