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Characterization of the Kaposi's sar...

Krithivas, Anita.

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Characterization of the Kaposi's sarcoma-associated herpesvirus latency-associated nuclear antigen: Roles in gene silencing and chromosome tethering.

Record Type:	Electronic resources : Monograph/item
Title/Author:	Characterization of the Kaposi's sarcoma-associated herpesvirus latency-associated nuclear antigen: Roles in gene silencing and chromosome tethering./
Author:	Krithivas, Anita.
Description:	227 p.
Notes:	Source: Dissertation Abstracts International, Volume: 63-10, Section: B, page: 4485.
Contained By:	Dissertation Abstracts International63-10B.
Subject:	Biology, Microbiology. -
Online resource:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3068177
ISBN:	0493877282

Characterization of the Kaposi's sarcoma-associated herpesvirus latency-associated nuclear antigen: Roles in gene silencing and chromosome tethering.
Krithivas, Anita.

Characterization of the Kaposi's sarcoma-associated herpesvirus latency-associated nuclear antigen: Roles in gene silencing and chromosome tethering. - 227 p.

Source: Dissertation Abstracts International, Volume: 63-10, Section: B, page: 4485.

Thesis (Ph.D.)--The Johns Hopkins University, 2003.

The Kaposi's sarcoma-associated herpesvirus (KSHV) is a gamma-2 herpesvirus which is associated with all forms of Kaposi's sarcoma (KS), primary effusion lymphoma (PEL), and some cases of multicentric Castleman's disease. KSHV is closely related to Epstein-Barr virus (EBV). KSHV encodes over ninety open reading frames consisting of captured cellular genes as well as novel proteins which play roles in tumorigenesis. Interestingly, it is the latent state of viral infection which is predominantly associated with disease. Only a few viral genes are expressed during viral latency including the latency-associated nuclear antigen (LANA). LANA is a large multifunctional protein with no known cellular homologs. LANA is similar to the EBV nuclear antigen 1 (EBNA1) in that it is required for latent episomal replication and for episomal maintenance.

ISBN: 0493877282Subjects--Topical Terms:

1017734
Biology, Microbiology.

Characterization of the Kaposi's sarcoma-associated herpesvirus latency-associated nuclear antigen: Roles in gene silencing and chromosome tethering.
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100 1 $a Krithivas, Anita. $3 1946982
245 1 0 $a Characterization of the Kaposi's sarcoma-associated herpesvirus latency-associated nuclear antigen: Roles in gene silencing and chromosome tethering.
300 $a 227 p.
500 $a Source: Dissertation Abstracts International, Volume: 63-10, Section: B, page: 4485.
500 $a Adviser: S. Diane Hayward.
502 $a Thesis (Ph.D.)--The Johns Hopkins University, 2003.
520 $a The Kaposi's sarcoma-associated herpesvirus (KSHV) is a gamma-2 herpesvirus which is associated with all forms of Kaposi's sarcoma (KS), primary effusion lymphoma (PEL), and some cases of multicentric Castleman's disease. KSHV is closely related to Epstein-Barr virus (EBV). KSHV encodes over ninety open reading frames consisting of captured cellular genes as well as novel proteins which play roles in tumorigenesis. Interestingly, it is the latent state of viral infection which is predominantly associated with disease. Only a few viral genes are expressed during viral latency including the latency-associated nuclear antigen (LANA). LANA is a large multifunctional protein with no known cellular homologs. LANA is similar to the EBV nuclear antigen 1 (EBNA1) in that it is required for latent episomal replication and for episomal maintenance.
520 $a New models of chromatin remodeling involving DNA and histone modifications, which are linked processes, and their effects on gene regulation have emerged over the past decade. Dysregulation of these cellular mechanisms has been implicated in cancers, particularly repression of tumor suppression genes via promoter hypermethylation. In this study, cellular promoter methylation changes upon KSHV infection were evaluated and the mechanism of gene silencing was investigated. Four promoters were shown to be methylated upon KSHV infection and one in particular, E-cadherin, was chosen for further investigation. An oncogenic viral protein, LANA, is described here to act as a transcriptional repressor via histone deacetylase-dependent mechanisms. LANA can repress EBV promoters and EBV protein expression which is consistent with the PEL phenotype. In addition, a novel repression mechanism for a viral protein involving recruitment of DNA methyltransferase Dnmt1 and methyl binding protein MeCP2 to specific tumor suppressor gene promoters, such as E-cadherin is provided. LANA can also repress the KSHV lytic switch protein Rta, thus providing a mechanism of how KSHV regulates its own life cycle.
520 $a The mechanism by which LANA supports episomal maintenance was investigated. LANA associates with chromosomes to tether viral episomes to them and ensure continuity of the viral life cycle after cell division. Two chromosome binding sites and the protein-protein interactions mediating chromosome tethering were established. Both MeCP2 and DEK were shown to tether LANA to chromosomes via two independent LANA binding domains.
590 $a School code: 0098.
650 4 $a Biology, Microbiology. $3 1017734
650 4 $a Health Sciences, Pharmacology. $3 1017717
650 4 $a Health Sciences, Oncology. $3 1018566
690 $a 0410
690 $a 0419
690 $a 0992
710 2 0 $a The Johns Hopkins University. $3 1017431
773 0 $t Dissertation Abstracts International $g 63-10B.
790 1 0 $a Hayward, S. Diane, $e advisor
790 $a 0098
791 $a Ph.D.
792 $a 2003
856 4 0 $u http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3068177