The Re1/-NF-KB family of transcription factors controls the growth and differentiation of vertebrate lymphoid cells, and mutant re1 genes have been associated with a number of lymphoid cancers in animals and humans. This work has had a continuing focus on understanding the cellular and molecular mechanisms by which Re1 transcription factors affect cell growth. In particular, the mechanism by which the v-Re1 oncoprotein of the avian Rev-T retrovirus induces malignant transformation and immortalization of avian lymphoid cells, and by which v-Re1 is toxic in mammalian cells will be investigated. Specifically, the following aims will be accomplished: a chicken re1B cDNA will be isolated and the ability of Re1B to interact with v-Re1 will be assessed; cDNAs encoding proteins that can interact with and modulate the activities to C-terminal sequences of v-Re1 will be identified and characterized; the effect of anti-apoptosis proteins on immortalization of cells by v-Re1 will be determined; the ability of v-Re1 mutants to induce toxicity in mammalian fibroblasts will be determined; as says will be developed to study the malignant transforming potential of other avian and mammalian Re1 proteins in avian and mammalian cells; and cellular genes whose expression is commonly altered in Re1-transformed cells will be identified. Furthermore, the mechanism by which certain Del proteins activate transcription will be investigated by determining what types of general transcription factors (such as transcriptional adapters) are needed for transcriptional activation by v-Re1, c-Re1, Re1A, and p85, an oncogenic form of NF-KB p100 found in HUT78 human leukemia cells. Together, these experiments will serve as models for understanding the molecular mechanisms underlying the development of a subset of human lymphoid malignancies.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
2R01CA047763-10A1
Application #
2405088
Study Section
Pathology B Study Section (PTHB)
Project Start
1988-09-01
Project End
2000-07-31
Budget Start
1997-08-01
Budget End
1998-07-31
Support Year
10
Fiscal Year
1997
Total Cost
Indirect Cost
Name
Boston University
Department
Type
Schools of Arts and Sciences
DUNS #
604483045
City
Boston
State
MA
Country
United States
Zip Code
02118
Haery, Leila; Mussakhan, Sultan; Waxman, David J et al. (2016) Evidence for an oncogenic modifier role for mutant histone acetyltransferases in diffuse large B-cell lymphoma. Leuk Lymphoma 57:2661-71
Gilmore, Thomas D; Gélinas, Céline (2015) Methods for assessing the in vitro transforming activity of NF-?B transcription factor c-Rel and related proteins. Methods Mol Biol 1280:427-46
Haery, Leila; Lugo-Picó, Julián G; Henry, Ryan A et al. (2014) Histone acetyltransferase-deficient p300 mutants in diffuse large B cell lymphoma have altered transcriptional regulatory activities and are required for optimal cell growth. Mol Cancer 13:29
Thompson, Ryan C; Vardinogiannis, Iosif; Gilmore, Thomas D (2013) Identification of an NF-?B p50/p65-responsive site in the human MIR155HG promoter. BMC Mol Biol 14:24
Thompson, Ryan C; Vardinogiannis, Iosif; Gilmore, Thomas D (2013) The sensitivity of diffuse large B-cell lymphoma cell lines to histone deacetylase inhibitor-induced apoptosis is modulated by BCL-2 family protein activity. PLoS One 8:e62822
Yeo, Alan T; Porco Jr, John A; Gilmore, Thomas D (2012) Bcl-XL, but not Bcl-2, can protect human B-lymphoma cell lines from parthenolide-induced apoptosis. Cancer Lett 318:53-60
Wolenski, Francis S; Chandani, Sushil; Stefanik, Derek J et al. (2011) Two polymorphic residues account for the differences in DNA binding and transcriptional activation by NF-?B proteins encoded by naturally occurring alleles in Nematostella vectensis. J Mol Evol 73:325-36
Wolenski, Francis S; Garbati, Michael R; Lubinski, Tristan J et al. (2011) Characterization of the core elements of the NF-?B signaling pathway of the sea anemone Nematostella vectensis. Mol Cell Biol 31:1076-87
Garbati, Michael R; Thompson, Ryan C; Haery, Leila et al. (2011) A rearranged EP300 gene in the human B-cell lymphoma cell line RC-K8 encodes a disabled transcriptional co-activator that contributes to cell growth and oncogenicity. Cancer Lett 302:76-83
Gilmore, Thomas D; Garbati, Michael R (2011) Inhibition of NF-?B signaling as a strategy in disease therapy. Curr Top Microbiol Immunol 349:245-63

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