Kaposi Sarcoma-associated Herpesvirus vIRF-3 Protein Binds to F-box of Skp2 Protein and Acts as a Regulator of c-Myc Protein Function and Stability

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11110%2F12%3A11736" target="_blank" >RIV/00216208:11110/12:11736 - isvavai.cz</a>

Výsledek na webu

<a href="http://dx.doi.org/10.1074/jbc.M111.335216" target="_blank" >http://dx.doi.org/10.1074/jbc.M111.335216</a>

DOI - Digital Object Identifier

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Jazyk výsledku

angličtina

Název v původním jazyce

Kaposi Sarcoma-associated Herpesvirus vIRF-3 Protein Binds to F-box of Skp2 Protein and Acts as a Regulator of c-Myc Protein Function and Stability

Popis výsledku v původním jazyce

The Kaposi sarcoma-associated herpesvirus (KSHV) has been linked to Kaposi sarcoma, body cavity-based lymphoma, and Castleman disease. vIRF-3 is a KSHV latent gene that is critical for proliferation of KSHV-positive lymphoid cells. Furthermore, vIRF-3 contributes to KSHV-associated pathogenesis by stimulating c-Myc transcription activity. Here we show that vIRF-3 can associate with Skp2, a key component of the SCFskp2 ubiquitin ligase complex. Skp2 is a transcriptional co-factor for c-Myc that was shownto regulate the stability of c-Myc protein as well as c-Myc-dependent transcription. In this study, we show that vIRF-3 binds to the F-box of Skp2 and recruits it to c-Myc-regulated promoters to activate c-Myc-dependent transcription. Additionally, cells overexpressing vIRF-3 exhibit higher levels of c-Myc ubiquitylation, suggesting that ubiquitylation is necessary for c-Myc-mediated transcription. Moreover, vIRF-3 can stabilize the c-Myc protein by increasing its half-life. Collectivel

Název v anglickém jazyce

Kaposi Sarcoma-associated Herpesvirus vIRF-3 Protein Binds to F-box of Skp2 Protein and Acts as a Regulator of c-Myc Protein Function and Stability

Popis výsledku anglicky

The Kaposi sarcoma-associated herpesvirus (KSHV) has been linked to Kaposi sarcoma, body cavity-based lymphoma, and Castleman disease. vIRF-3 is a KSHV latent gene that is critical for proliferation of KSHV-positive lymphoid cells. Furthermore, vIRF-3 contributes to KSHV-associated pathogenesis by stimulating c-Myc transcription activity. Here we show that vIRF-3 can associate with Skp2, a key component of the SCFskp2 ubiquitin ligase complex. Skp2 is a transcriptional co-factor for c-Myc that was shownto regulate the stability of c-Myc protein as well as c-Myc-dependent transcription. In this study, we show that vIRF-3 binds to the F-box of Skp2 and recruits it to c-Myc-regulated promoters to activate c-Myc-dependent transcription. Additionally, cells overexpressing vIRF-3 exhibit higher levels of c-Myc ubiquitylation, suggesting that ubiquitylation is necessary for c-Myc-mediated transcription. Moreover, vIRF-3 can stabilize the c-Myc protein by increasing its half-life. Collectivel

Druh

J_x - Nezařazeno - Článek v odborném periodiku (Jimp, Jsc a Jost)

CEP obor

EE - Mikrobiologie, virologie

OECD FORD obor

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Projekt

<a href="/cs/project/GA204%2F09%2F0773" target="_blank" >GA204/09/0773: Využití metody RNA interference (RNAi) v studiu onkogenních vlastností vIRF-3, který je kódovaný virem Kaposiho sarkomu (KSHV)</a><br>

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)<br>Z - Vyzkumny zamer (s odkazem do CEZ)<br>S - Specificky vyzkum na vysokych skolach

Rok uplatnění

2012

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Journal of Biological Chemistry

ISSN

0021-9258

e-ISSN

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Svazek periodika

287

Číslo periodika v rámci svazku

20

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

10

Strana od-do

16199-16208

Kód UT WoS článku

000304030900012

EID výsledku v databázi Scopus

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