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.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
- natural sciences biological sciences microbiology virology
- medical and health sciences clinical medicine oncology breast cancer
You need to log in or register to use this function
We are sorry... an unexpected error occurred during execution.
You need to be authenticated. Your session might have expired.
Thank you for your feedback. You will soon receive an email to confirm the submission. If you have selected to be notified about the reporting status, you will also be contacted when the reporting status will change.
Programme(s)
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Topic(s)
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Call for proposal
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
FP7-PEOPLE-2013-IIF
See other projects for this call
Funding Scheme
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
Coordinator
30625 Hannover
Germany
The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.