CORDIS
EU research results

CORDIS

English EN

Regulation and function of the E3 ubiquitin ligases Muscle RING finger 1 and 3 in cardiac hypertrophy

Project information

Grant agreement ID: 231014

Status

Closed project

  • Start date

    1 January 2010

  • End date

    31 December 2013

Funded under:

FP7-PEOPLE

  • Overall budget:

    € 100 000

  • EU contribution

    € 100 000

Coordinated by:

MAX DELBRUECK CENTRUM FUER MOLEKULARE MEDIZIN IN DER HELMHOLTZ-GEMEINSCHAFT (MDC)

Germany

Objective

Heart failure caused by cardiac hypertrophy is a growing epidemic and remains the most frequent cause of hospitalization in elderly patients in the European Union. However, molecular mechanisms leading to cardiac hypertrophy and its transition into heart failure are poorly understood. Maintenance of cardiac structure and function requires a precise control of protein synthesis and degradation; abnormalities in these processes can give rise to myopathies. The protein degrading ubiquitin proteasome system (UPS) and its muscle specific key enzymes Muscle RING finger (MuRF) 1 and 3 are activated during cardiac hypertrophy and heart failure. MuRF1 and 3 are essential for the degradation of structural proteins, such as myosin heavy chain (MHC), leading to a decrease in cardiac function and heart failure. MuRF inhibitors are therefore expected to prevent transition of cardiac hypertrophy into failure. This proposal aims to investigate the function and regulation of MuRF1 and 3 during cardiac hypertrophy. More specifically, the major hypothesis that the function of MuRF1 is mainly mediated through its E3 ubiquitin ligase activity will be investigated. First, the specific cysteine residue within the RING-finger of MuRF1 responsible for its E3 ubiquitin ligase activity will be identified. This residue will than be germ-line mutated and the hypertrophic response of mice lacking MuRF1s E3 ligase activity will be analyzed following aortic banding. Secondly, the domains within MuRF proteins mediating MuRF binding to their MHC target proteins will be investigated. Additionally, we aim to analyze if hypertrophic stimuli can regulate binding between MuRF1 and 3 and their target proteins. Finally, a cDNA expression screen will be employed to discover novel transcription factors and signal transduction pathways regulating MuRF1 expression during hypertrophy. Furthermore, our preliminary data showed that the MuRF1 promoter can be activated through the muscle-specific transcription fac

Coordinator

MAX DELBRUECK CENTRUM FUER MOLEKULARE MEDIZIN IN DER HELMHOLTZ-GEMEINSCHAFT (MDC)

Address

Robert Rossle Strasse 10
13125 Berlin

Germany

Activity type

Research Organisations

EU Contribution

€ 100 000

Administrative Contact

Andrea Winnefeld (Mr.)

Project information

Grant agreement ID: 231014

Status

Closed project

  • Start date

    1 January 2010

  • End date

    31 December 2013

Funded under:

FP7-PEOPLE

  • Overall budget:

    € 100 000

  • EU contribution

    € 100 000

Coordinated by:

MAX DELBRUECK CENTRUM FUER MOLEKULARE MEDIZIN IN DER HELMHOLTZ-GEMEINSCHAFT (MDC)

Germany