RSM BCA2

CHARACTERIZATION OF THE ANTIVIRAL ACTIVITY OF BCA2

Coordinatore	MEDIZINISCHE HOCHSCHULE HANNOVER    more  Organization address address: Carl-Neuberg-Strasse 1 city: HANNOVER postcode: 30625 contact info Titolo: Mr. Nome: Frank Cognome: Dittrich Email: send email Telefono: +49 5115325343
Nazionalità Coordinatore	Germany [DE]
Totale costo	161˙968 €
EC contributo	161˙968 €
Programma	FP7-PEOPLE Specific programme "People" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013)
Code Call	FP7-PEOPLE-2013-IIF
Funding Scheme	MC-IIF
Anno di inizio	0
Periodo (anno-mese-giorno)	0000-00-00   -   0000-00-00

 Partecipanti

#	participant	country	role	EC contrib. [€]
1	MEDIZINISCHE HOCHSCHULE HANNOVER  Organization address address: Carl-Neuberg-Strasse 1 city: HANNOVER postcode: 30625 contact info Titolo: Mr. Nome: Frank Cognome: Dittrich Email: send email Telefono: +49 5115325343	DE (HANNOVER)	coordinator	161˙968.80

Mappa

 Word cloud

Esplora la "nuvola delle parole (Word Cloud) per avere un'idea di massima del progetto.

 Obiettivo del progetto (Objective)

'BCA2 (Breast Cancer-Associated gene 2, also known as RNF115, ZNF364 or Rabring7) is a cytoplasmic RING-finger E3 ubiquitin ligase that is upregulated in most breast cancer cell lines in response to estrogen. A recent study showed that BCA2 interacts with the cytoplasmic domain of tetherin/BST2 to promote the internalization and degradation of tethered HIV-1 particles, and that the E3 ligase activity of BCA2 is dispensable to enhance the tetherin-mediated restriction of HIV-1. Therefore, BCA2 would act as a tetherin co-factor, lacking antiviral activity in cells not expressing tetherin. However, here we show for the first time that BCA2 also inhibits virus production in a tetherin-independent manner by reducing the cellular levels of HIV-1 Gag, and that this activity requires the E3 ligase activity. Furthermore, we show that BCA2 physically interacts with Gag and promotes its ubiquitination and lysosomal degradation, suggesting that BCA2 may be an innate antiviral factor that impedes virus assembly and release. We want to formally address this hypothesis by characterizing the molecular mechanism(s) of the tetherin-dependent and tetherin-independent antiviral activity of BCA2 (Specific Aim 1) and by identifying the molecules and cellular pathways that participate in the regulation of BCA2’s activity (Specific Aim 2). A better understanding of the innate mechanisms that limit virus production will help in the elaboration of antiretroviral drugs to contain virus replication in affected individuals. Therefore, the objectives outlined here are directly relevant to identifying new targets for antiretroviral therapy to control HIV-1 infection.'