Abstract

Although there is a great deal known about the transport of proteins into the nucleus, little is known about the mechanisms that direct DNA molecules within this organelle. Recent experimental findings by the PI have suggested that the genomes of large DNA viruses are deposited in or adjacent to defined domains called N10 within the nucleus. Within these domains, virus replication and transcription can begin without the expression of other virus proteins. If N10 domains can be shown to be the obligatory target of large DNA virus genomes, then strategies to block this targeted transport could prevent virus replication. The applicant will construct cell lines in which the N10 target has been eliminated, to test this hypothesis.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Exploratory/Developmental Grants (R21)
Project #
5R21GM057599-02
Application #
6017129
Study Section
Experimental Virology Study Section (EVR)
Project Start
1998-06-01
Project End
2000-05-31
Budget Start
1999-06-01
Budget End
2000-05-31
Support Year
2
Fiscal Year
1999
Total Cost
Indirect Cost

  Institution

Name
Wistar Institute
Department
Type
DUNS #
042250712
City
Philadelphia
State
PA
Country
United States
Zip Code
19104

  Publications

Negorev, Dmitri G; Vladimirova, Olga V; Kossenkov, Andrew V et al. (2010) Sp100 as a potent tumor suppressor: accelerated senescence and rapid malignant transformation of human fibroblasts through modulation of an embryonic stem cell program. Cancer Res 70:9991-10001
Ivanov, Alexey V; Peng, Hongzhuang; Yurchenko, Vyacheslav et al. (2007) PHD domain-mediated E3 ligase activity directs intramolecular sumoylation of an adjacent bromodomain required for gene silencing. Mol Cell 28:823-37
Tang, Qiyi; Murphy, Eain A; Maul, Gerd G (2006) Experimental confirmation of global murine cytomegalovirus open reading frames by transcriptional detection and partial characterization of newly described gene products. J Virol 80:6873-82
Negorev, Dmitri G; Vladimirova, Olga V; Ivanov, Alexey et al. (2006) Differential role of Sp100 isoforms in interferon-mediated repression of herpes simplex virus type 1 immediate-early protein expression. J Virol 80:8019-29
Tang, Qiyi; Maul, Gerd G (2006) Mouse cytomegalovirus crosses the species barrier with help from a few human cytomegalovirus proteins. J Virol 80:7510-21
Tang, Qiyi; Li, Luge; Maul, Gerd G (2005) Mouse cytomegalovirus early M112/113 proteins control the repressive effect of IE3 on the major immediate-early promoter. J Virol 79:257-63
Ishov, Alexander M; Vladimirova, Olga V; Maul, Gerd G (2004) Heterochromatin and ND10 are cell-cycle regulated and phosphorylation-dependent alternate nuclear sites of the transcription repressor Daxx and SWI/SNF protein ATRX. J Cell Sci 117:3807-20
Nefkens, Isabelle; Negorev, Dmitri G; Ishov, Alexander M et al. (2003) Heat shock and Cd2+ exposure regulate PML and Daxx release from ND10 by independent mechanisms that modify the induction of heat-shock proteins 70 and 25 differently. J Cell Sci 116:513-24
Bell, P; Montaner, L J; Maul, G G (2001) Accumulation and intranuclear distribution of unintegrated human immunodeficiency virus type 1 DNA. J Virol 75:7683-91
Negorev, D; Ishov, A M; Maul, G G (2001) Evidence for separate ND10-binding and homo-oligomerization domains of Sp100. J Cell Sci 114:59-68

Showing the most recent 10 out of 16 publications