Objective
Deregulated expression of MYC or one of its paralogues, MYCN and MYCL, maintains the growth of most human tumors. All current models explain the oncogenic potential of MYC proteins by their ability to form complexes with MAX that universally bind to active promoters and the ability of these complexes to induce a tumor-specific gene expression pattern.
While MYC conforms to this model during unperturbed cell growth, we have discovered two paradigmatic situations in which MYC proteins undergo fundamental changes in their biochemical state, association with MAX and localization on chromatin: In response to pharmacological or physical disruption of transcription elongation, MYC moves away from active promoters to form large, spherical multimers that surround stalled replication forks. These multimers contain transcription termination factors and form a zone that shields stalled forks from RNA polymerase. Second, MYCN forms high molecular weight complexes during the S phase of the cell cycle that do not contain MAX and, like MYC multimers, contain termination factors. Their assembly depends on RNA that is normally degraded by the nuclear exosome, arguing that they too form in response to aberrant transcription. The switch between heterodimeric and multimeric states depends on non-proteolytic ubiquitylation of MYC, which alters protein-protein interactions that retain MYC at promoters.
Our data show that MYC proteins exist in a hitherto unknown dynamic equilibrium between globally promoter-bound heterodimers and multimers that form locally in response to perturbed transcription. We aim to show that these dynamics enable tumor cells to cope with stress arising from deregulated transcription and are crucial for MYC´s oncogenic function. We expect that inhibiting MYC multimerization will maintain normal growth but block the ability of tumour cells to cope with deregulated transcription and is therefore a valid therapeutic strategy for targeting oncogenic functions of MYC
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 biochemistry biomolecules proteins
- natural sciences biological sciences genetics RNA
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Keywords
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
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.
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HORIZON.1.1 - European Research Council (ERC)
MAIN PROGRAMME
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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.
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.
HORIZON-ERC - HORIZON ERC Grants
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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.
(opens in new window) ERC-2022-ADG
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Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.
97070 Wuerzburg
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.