Cracking the SUMO Signalling Code

Obiettivo

"Functional activity of proteins is tightly controlled via reversible post-translational modifications including phosphorylation, acetylation and ubiquitylation. These modifications enable the orchestration of cellular responses to a wide variety of stimuli. Due to these modifications, proteomes are overwhelmingly complex. Progress in the field has been greatly accelerated by the development of novel approaches to study these post-translational modifications at a proteome-wide scale using the sensitivity and robustness of mass spectrometry (MS). This has enabled the identification of thousands of dynamically regulated phosphorylation, acetylation and ubiquitylation sites by MS. The functional significance of these modifications is now being addressed worldwide at an unprecedented scale. In contrast, global understanding of ubiquitin-like signalling networks in a site-specific manner is very challenging.

Over the last few years, my lab has established novel methodology for the purification and identification of endogenous SUMO target proteins and SUMOylation sites of endogenous targets. The first aim of this project is to uncover small ubiquitin-like modifier (SUMO) signalling pathways in a site-specific manner at a proteome-wide level.

The second aim of this project is to reveal how SUMOylation cooperates with ubiquitylation to maintain genome integrity. SUMOylation plays a critical role during the DNA damage response, an important barrier against genome instability linked diseases including cancer and neurodegeneration. Selected target proteins will be studied at the functional and mechanistic level to obtain novel insight in cellular processes that protect against genome instability.

The developed methodology is generic and can be applied to study all ubiquitin-like proteins at a proteome-wide level in a site-specific manner, enabling global understanding of ubiquitin-like signalling networks in health and disease."

Campo scientifico

Meccanismo di finanziamento

ERC-SG - ERC Starting Grant

Istituzione ospitante

ACADEMISCH ZIEKENHUIS LEIDEN

Contributo UE

€ 1 517 698,80

Indirizzo

ALBINUSDREEF 2
2333 ZA Leiden
Paesi Bassi

Regione

West-Nederland Zuid-Holland Agglomeratie Leiden en Bollenstreek

Tipo di attività

Higher or Secondary Education Establishments

Contatto amministrativo

Karin Wibier (Ms.)

Ricercatore principale

Alfredus Cornelis Otto Vertegaal (Dr.)

Collegamenti

Contatta l’organizzazione Sito web

Costo totale

Nessun dato

Beneficiari (1)