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Strict control over degradation of individual proteins at the correct time and space in cells is key for dynamic transitions in cell signaling. Protein modification by the modifier ubiquitin is recognized as a fundamental mechanism to target proteins to the main protease complex in the cell: the proteasome. Cell-free and structural studies have provided mechanistic insight into how ubiquitinated proteins are recognized and degraded by the proteasome. However, many principles and regulators of how ubiquitination, proteasome targeting, target extraction from sub-cellular sites, and fate-determinations at the proteasome in the crowded intracellular space are achieved, remain unknown.
Main questions addressed are: 1) How are immune- and cancer-associated proteins targeted to the proteasome, 2) which other cellular factors control their degradation, 3) are these processes deregulated in cancer and immune disease, and 4) how do they mechanistically determine cellular protein fate decisions?
To identify novel cellular regulators of proteasome-dependent degradation, the Versteeg lab utilizes genome-wide genetic screening approaches. There is a strong focus on the discovery of factors controlling the degradation of disease-associated proteins with different conceptual properties, such as ubiquitin-independent, and activation-coupled proteasomal degradation. Following identification of key players in protein stability, we aim to determine the molecular mechanisms by which these regulators control degradation of their targets using cell-biology approaches, and biochemical in vitro reconstitution.
Gijs Versteeg studied Biomedical Sciences, and obtained his PhD in Molecular Virology at the University of Leiden, The Netherlands. He further continued his research on cellular immune signaling responses as a post-doctoral fellow in the Influenza Center of Excellence at Mount Sinai School of Medicine in New York City. Gijs started his independent research group at the Max Perutz Labs in 2013.
Most cellular proteins are present in the majority of mammals, and are essential for life. Yet, few of them are only found in humans, and often have non-essential functions. We recently discovered that a human-specific –non-conserved– RING protein is essential for cancer cells. Its genetic deletion de-represses a cellular stress response, thereby bringing a stop to cell division.
Unstructured regions with a diverse amino acid composition in proteins are key for initiating proteasomal degradation. Consequently, repetitive sequences are poor degradation-initiation sites. We recently discovered one of the most unstable proteins in human cells with a three-minute half-life. Unexpectedly, its extreme instability is dependent on a large, repetitive protein loop.
Unanchored K48-Linked Polyubiquitin Synthesized by the E3-Ubiquitin Ligase TRIM6 Stimulates the Interferon-IKKε Kinase-Mediated Antiviral Response.
Rajsbaum, Ricardo; Versteeg, Gijs A; Schmid, Sonja; Maestre, Ana M; Belicha-Villanueva, Alan; Martínez-Romero, Carles; Patel, Jenish R; Morrison, Juliet; Pisanelli, Giuseppe; Miorin, Lisa; Laurent-Rolle, Maudry; Moulton, Hong M; Stein, David A; Fernandez-Sesma, Ana; tenOever, Benjamin R; García-Sastre, Adolfo
The E3-ligase TRIM family of proteins regulates signaling pathways triggered by innate immune pattern-recognition receptors.
Versteeg, Gijs A; Rajsbaum, Ricardo; Sánchez-Aparicio, Maria Teresa; Maestre, Ana M; Valdiviezo, Julio; Shi, Mude; Inn, Kyung-Soo; Fernandez-Sesma, Ana; Jung, Jae; García-Sastre, Adolfo
Chemical inhibition of RNA viruses reveals REDD1 as a host defense factor.
Mata, Miguel A; Satterly, Neal; Versteeg, Gijs A; Frantz, Doug; Wei, Shuguang; Williams, Noelle; Schmolke, Mirco; Peña-Llopis, Samuel; Brugarolas, James; Forst, Christian V; White, Michael A; García-Sastre, Adolfo; Roth, Michael G; Fontoura, Beatriz M A
The Group Versteeg is a member of the special Doctoral Program "Signaling Mechanisms in Cellular Homeostasis" reviewed and funded by the Austrian Research Fund FWF.
Project title: "Inhibition of macrophage activation by TRIM47"
The Versteeg group is associated with the Vienna Doctoral School: PhD track Signaling Mechanisms in Cellular Homeastasis.
Project title: "Inhibition of the antiviral immune response by TRIM52"
18th Microsymposium on RNA Biology
The „Microsymposium on RNA Biology“ is an international conference that brings together young scientists, junior and senior group leaders, and company representatives from all over the world to present and discuss their latest findings in the exciting field of small RNAs and beyond. The Microsymposium was founded in 2005 and has established itself as the major small RNA meeting in Europe. It is organized by the four research institutions IMBA, IMP, GMI and the Max Perutz Labs as well as by the RNA community of the Vienna BioCenter.
Transformation Reactions of Organic Contaminants and Oxygen: From Field Sites to Reaction Mechanisms
Nickel impact on human health, from bacterial infections to cancer
Multiscale plant bioimaging using advanced microscopy
Parthenogenesis, cryptobiosis, and the survival in extreme environmental conditions
Evading ageing: Mitochondrial and proteostatic adaptations in oocytes
Genomes in Rhodnius prolixus symbiotic system
Stem cells, immune evasion and metastasis in colorectal cancer
Ubiquitin & Friends Symposium 2024
The Ubiquitin & Friends Symposium is an annual international meeting taking place in the beautiful capital of Austria, aiming to bring together scholars from various fields studying ubiquitin/Ubl biology and protein degradation in a personal, family-like atmosphere, as suggested by the name.
The evolution and development of mollusc shells
Unraveling the Complexity of Crossover Regulation in C. elegans
Dynamics of 3D Genome Structure and Function
How superworms can help to solve our plastic waste crisis
Title to be announced
New players in an old pathway: biology of methanogens of the TACK superphylum
Shaping morphogen gradients: from molecules to tissues and back
Title to be announced
Studying stressed cells by in situ structural biology
Exploring Microbial Resilience: Unravelling Escherichia coliand#x27;s Stress Response at the Level of Protein Synthesis
Arbuscular mycorrhiza development and function
Deep homology and deep diversity: Evolving genetic toolkits for making and sensing light
The evolution of cell type identity and tissue microecology at the fetal-maternal interface
The unanticipated roles of PICIs and phages in bacterial evolution
Chemical targeting of subcellular protein localization
Origin and diversification of gut-derived organs in chordates
Job's Dilemma for the Genome: Why Bad Things Happen to Good Chromosomes
Connections between carbon and nitrogen cycling in the ocean
Understanding how the DNA-loop-extruding protein complex Condensin folds a chromatinized genome into mitotic chromosomes
From Roads to Rivers? Occurrence and environmental fate of tire and road wear particles and of tire-related chemicals
FENS 2024 Satellite event: Home cage behavior monitoring at the interface of animal welfare and neuroscience
Striking physiology and cell biology of (marine) environmental microorganisms
Mechanisms controlling maintenance of cohesin dependent loops
Title to be announced