KSHV-Mediated Regulation of Par3 and SNAIL Contributes to B-Cell Proliferation
Publication Date
July 27, 2016
Journal
PLOS Pathogens
Authors
Hem C. Jha, Zhiguo Sun, Santosh K. Upadhyay, Darine W. El Naccache, et al
Volume
12
Issue
7
Pages
e1005801
DOI
https://dx.plos.org/10.1371/journal.ppat.1005801
Publisher URL
http://journals.plos.org/plospathogens/article?id=10.1371%2Fjournal.ppat.1005801
Scopus
84980584563
Mendeley
http://www.mendeley.com/research/kshvmediated-regulation-par3-snail-contributes-bcell-proliferation
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Mendeley | Further Information

{"title"=>"KSHV-Mediated Regulation of Par3 and SNAIL Contributes to B-Cell Proliferation", "type"=>"journal", "authors"=>[{"first_name"=>"Hem C.", "last_name"=>"Jha", "scopus_author_id"=>"35487831000"}, {"first_name"=>"Zhiguo", "last_name"=>"Sun", "scopus_author_id"=>"56084558400"}, {"first_name"=>"Santosh K.", "last_name"=>"Upadhyay", "scopus_author_id"=>"57093194700"}, {"first_name"=>"Darine W.", "last_name"=>"El-Naccache", "scopus_author_id"=>"55655217700"}, {"first_name"=>"Rajnish K.", "last_name"=>"Singh", "scopus_author_id"=>"57190752214"}, {"first_name"=>"Sushil K.", "last_name"=>"Sahu", "scopus_author_id"=>"37012318600"}, {"first_name"=>"Erle S.", "last_name"=>"Robertson", "scopus_author_id"=>"35552175300"}], "year"=>2016, "source"=>"PLoS Pathogens", "identifiers"=>{"issn"=>"15537374", "sgr"=>"84982883845", "doi"=>"10.1371/journal.ppat.1005801", "scopus"=>"2-s2.0-84982883845", "isbn"=>"1553-7374 (Electronic)\r1553-7366 (Linking)", "pmid"=>"27463802", "pui"=>"611581985"}, "id"=>"fb0912a7-4820-3108-bc4c-bd67909c917d", "abstract"=>"Studies have suggested that Epithelial-Mesenchymal Transition (EMT) and transformation is an important step in progression to cancer. Par3 (partitioning-defective protein) is a crucial factor in regulating epithelial cell polarity. However, the mechanism by which the latency associated nuclear antigen (LANA) encoded by Kaposi's Sarcoma associated herpesvirus (KSHV) regulates Par3 and EMTs markers (Epithelial-Mesenchymal Transition) during viral-mediated B-cell oncogenesis has not been fully explored. Moreover, several studies have demonstrated a crucial role for EMT markers during B-cell malignancies. In this study, we demonstrate that Par3 is significantly up-regulated in KSHV-infected primary B-cells. Further, Par3 interacted with LANA in KSHV positive and LANA expressing cells which led to translocation of Par3 from the cell periphery to a predominantly nuclear signal. Par3 knockdown led to reduced cell proliferation and increased apoptotic induction. Levels of SNAIL was elevated, and E-cadherin was reduced in the presence of LANA or Par3. Interestingly, KSHV infection in primary B-cells led to enhancement of SNAIL and down-regulation of E-cadherin in a temporal manner. Importantly, knockdown of SNAIL, a major EMT regulator, in KSHV cells resulted in reduced expression of LANA, Par3, and enhanced E-cadherin. Also, SNAIL bound to the promoter region of p21 and can regulate its activity. Further a SNAIL inhibitor diminished NF-kB signaling through upregulation of Caspase3 in KSHV positive cells in vitro. This was also supported by upregulation of SNAIL and Par3 in BC-3 transplanted NOD-SCID mice which has potential as a therapeutic target for KSHV-associated B-cell lymphomas.", "link"=>"http://www.mendeley.com/research/kshvmediated-regulation-par3-snail-contributes-bcell-proliferation", "reader_count"=>12, "reader_count_by_academic_status"=>{"Unspecified"=>2, "Researcher"=>2, "Student > Doctoral Student"=>2, "Student > Ph. D. Student"=>2, "Student > Postgraduate"=>1, "Other"=>1, "Student > Bachelor"=>2}, "reader_count_by_user_role"=>{"Unspecified"=>2, "Researcher"=>2, "Student > Doctoral Student"=>2, "Student > Ph. D. Student"=>2, "Student > Postgraduate"=>1, "Other"=>1, "Student > Bachelor"=>2}, "reader_count_by_subject_area"=>{"Unspecified"=>4, "Biochemistry, Genetics and Molecular Biology"=>4, "Agricultural and Biological Sciences"=>2, "Immunology and Microbiology"=>2}, "reader_count_by_subdiscipline"=>{"Immunology and Microbiology"=>{"Immunology and Microbiology"=>2}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>2}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>4}, "Unspecified"=>{"Unspecified"=>4}}, "group_count"=>0}

Scopus | Further Information

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