INTRODUCTION AND BACKGROUND. The Research Career Award to Professor Maurice Green for the past 46 years is greatly appreciated by the University. The Award has allowed a distinguished faculty member of the Saint Louis University Medical School to develop an outstanding research program and to establish and strengthen the Institute for Molecular Virology, a center for research and training in cancer biology, tumor virology, and AIDS research. Because of his Research Career Award, the greater part of Dr. Green?s administrative duties in the operation of the Institute are delegated to a Business Administrator and to an Office Manager. Dr. Green's major activity continues to be research and teaching. In addition to conducting and directing his research program, he lectures on tumor virology and oncology to medical students and participates in the Core interdepartmental graduate training program on Cell and Molecular Biology. Dr. Green serves on the Executive Faculty Committee, on the Dean's Chairmen's Committee and on the Dean?s Research Planning Committee of the School of Medicine as well as on the Internal Advisory Board of the Cancer Center. The laboratory of Dr. Maurice Green has made many seminal contributions which have helped to develop the human adenoviruses (Ad) as prototype systems to study virus replication, cell transformation, and the molecular biology of the human cell. Because of these early studies, Ads have become powerful and important model systems that are used worldwide. Dr. Green continues to have an innovative research program which focuses on the oncoproteins encoded by Ad early region 1A (E1A). E1A functions are essential for efficient adenovirus replication in human cells. Towards this end, E1A has evolved protein sequences that interact with pivotal cellular transcription regulatory proteins and cellular gene promoters to control cell cycle progression, cell differentiation, and chromatin remodeling. E1A proteins encode multiple independent domains with diverse biochemical and biological functions including transcriptionalactivation, transcriptional-repression, induction of cellular DNA synthesis, cell immortalization, cell transformation as well as, paradoxically, the inhibition of metastasis and cell differentiation. We have a limited understanding of the specific molecular mechanisms and the precise role of cellular regulatory factors in these processes. The systematic study of E1A functional activities provides important opportunities to explore important and complex questions in cell growth regulation, oncogenesis, and virus control.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Career Awards (K06)
Project #
5K06AI004739-52
Application #
8536722
Study Section
Special Emphasis Panel (NSS)
Program Officer
Park, Eun-Chung
Project Start
1977-09-01
Project End
2017-08-31
Budget Start
2013-09-01
Budget End
2014-08-31
Support Year
52
Fiscal Year
2013
Total Cost
$33,939
Indirect Cost
$2,514
Name
Saint Louis University
Department
Microbiology/Immun/Virology
Type
Schools of Medicine
DUNS #
050220722
City
Saint Louis
State
MO
Country
United States
Zip Code
63103
Zhao, Ling-Jun; Loewenstein, Paul M; Green, Maurice (2017) Enhanced MYC association with the NuA4 histone acetyltransferase complex mediated by the adenovirus E1A N-terminal domain activates a subset of MYC target genes highly expressed in cancer cells. Genes Cancer 8:752-761
Zhao, Ling-Jun; Loewenstein, Paul M; Green, Maurice (2017) Adenovirus E1A TRRAP-targeting domain-mediated enhancement of MYC association with the NuA4 complex activates a panel of MYC target genes enriched for gene expression and ribosome biogenesis. Virology 512:172-179
Zhao, Ling-Jun; Loewenstein, Paul M; Green, Maurice (2016) Ad E1A 243R oncoprotein promotes association of proto-oncogene product MYC with the NuA4/Tip60 complex via the E1A N-terminal repression domain. Virology 499:178-184
Zhao, Ling-Jun; Loewenstein, Paul M; Green, Maurice (2016) The adenoviral E1A N-terminal domain represses MYC transcription in human cancer cells by targeting both p300 and TRRAP and inhibiting MYC promoter acetylation of H3K18 and H4K16. Genes Cancer 7:98-109
Loewenstein, Paul M; Wu, Shwu-Yuan; Chiang, Cheng-Ming et al. (2012) The adenovirus E1A N-terminal repression domain represses transcription from a chromatin template in vitro. Virology 428:70-5
Loewenstein, Paul M; Green, Maurice (2011) Expression of the Adenovirus Early Gene 1A Transcription-Repression Domain Alone Downregulates HER2 and Results in the Death of Human Breast Cancer Cells Upregulated for the HER2 Proto-Oncogene. Genes Cancer 2:737-44
Green, Maurice; Panesar, Ninder K; Loewenstein, Paul M (2008) Adenovirus E1A proteins are closely associated with chromatin in productively infected and transformed cells. Virology 371:1-7
Weeks, B S; Desai, K; Loewenstein, P M et al. (1993) Identification of a novel cell attachment domain in the HIV-1 Tat protein and its 90-kDa cell surface binding protein. J Biol Chem 268:5279-84
Kamine, J; Loewenstein, P; Green, M (1991) Mapping of HIV-1 Tat protein sequences required for binding to Tar RNA. Virology 182:570-7
Rawls, J A; Pusztai, R; Green, M (1990) Chemical synthesis of human papillomavirus type 16 E7 oncoprotein: autonomous protein domains for induction of cellular DNA synthesis and for trans activation. J Virol 64:6121-9

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