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Title panel depicting logo of the DEGRADATOR game, logos of the Pokrzywa Laboratory and International Institute of Molecular and Cell Biology in Warsaw - IIMCB and several game characters

Learn the fascinating science of protein
degradation with our computer game

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Have fun exploring the mechanisms of protein degradation in our educational computer game and discover the science behind the ubiquitin-proteasome system that eliminates abnormal proteins in our cells. Learn also about targeted protein degradation, an innovative method of destroying pathogenic proteins using our own cellular degradation pathways.

Join us to learn, play, and uncover the secrets of cellular life!

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Protein degradation

Discover the science behind the destruction of proteins and its implications for cell function and new therapies

The Art Of Keeping Balance

Graphic of scale, where the left pan shows the process of protein synthesis by the ribosome, and the right pan shows small fragments of degraded protein
The balance between protein synthesis and degradation is essential for proper cellular function: left – protein synthesis is shown by the ribosome forming an amino acid chain based on mRNA (messenger RNA; matrix RNA); right – protein degradation is shown as a protein broken down into short amino acid chains.

Proteins are molecules responsible for performing many essential functions in the cell. Their formation begins with the transcription of DNA into messenger RNA (mRNA) in a process called transcription. The synthesized mRNA molecule then serves as a template for protein synthesis, termed translation, which takes place with the help of ribosomes. During translation, amino acids combine into a polypeptide chain, which forms a functional protein structure. A human cell can produce up to approximately 20,000 different proteins.

Maintaining protein homeostasis (equilibrium) requires efficient mechanisms for protein degradation. Every protein persists in a cell for a certain period, from seconds to minutes or even years. However, proteins can form incorrectly or contain the wrong amino acids, making their timely and accurate removal essential for proper cell function. The main pathway responsible for protein degradation is the ubiquitin-proteasome system (UPS).

Graphic of scale, where the left pan shows the process of protein synthesis by the ribosome, and the right pan shows small fragments of degraded protein
The balance between protein synthesis and degradation is essential for proper cellular function: left – protein synthesis is shown by the ribosome forming an amino acid chain based on mRNA (messenger RNA; matrix RNA); right – protein degradation is shown as a protein broken down into short amino acid chains.
Graphic of the ubiquitin-proteasome system pathway
The UPS uses a cascade of enzymes to selectively label proteins with ubiquitin, allowing the proteasome to degrade them.

Ubiquitin-Proteasome System

Graphic of the ubiquitin-proteasome system pathway
The UPS uses a cascade of enzymes to selectively label proteins with ubiquitin, allowing the proteasome to degrade them.

In our game, we show the functioning of the ubiquitin-proteasome system (UPS). It involves a cascade of enzymes that includes E1, the ubiquitin-activating enzyme; E2, the ubiquitin-conjugating enzyme; and E3, the ubiquitin ligase, which work together to attach ubiquitin to the target protein. This process, called ubiquitination, results in proteins being recognized and then degraded by the proteasome. The proteasome acts as a cellular recycling center, breaking down ubiquitin-tagged proteins into short amino acid chains that can be reused by the cell to, for example, synthesize new proteins.

The UPS plays an important role in maintaining protein homeostasis by controlling protein levels and eliminating those that are unwanted. In this way, it regulates various molecular processes, such as the cell cycle, signal transduction, and DNA repair. Mutations of UPS components can lead to protein accumulation, disrupt cellular functions, and contribute to the development of various diseases, including cancer, Alzheimer’s disease, and Parkinson’s disease.

Targeted Protein Degradation - The Future Of Medicine?

Graphic of E2-E3 enzymes' complex where E2 is carrying ubiquitin and E3 is bound to substrate via a PROTAC compound
Molecular glues and PROTACs are two different approaches to targeted protein degradation; molecular glues are small molecules that enhance the interaction between the E3 ligase and the target protein; PROTACs are compounds composed of two components, in which one part recognizes the specific E3 ligase and the other part recognizes the selected target protein. Both approaches result in ubiquitination of the target protein and ultimately lead to its degradation.

What if we could harness our ubiquitin-proteasome system and tailor it to remove toxic disease-causing proteins? Well, this is no longer science fiction – it is how modern targeted protein degradation (TPD) therapies work. The strategy is simple; scientists design compounds that allow E3 ligases to bind proteins that they don’t normally recognize. The E3 ligases then bring them to E2 enzymes, resulting in ubiquitination of the proteins and degradation by the proteasome.

The two main classes of compounds using targeted protein degradation mechanisms are molecular glues and PROTACs. Molecular glues are small molecules that enhance interactions between an E3 ligase and a selected protein, while PROteolysis TArgeting Chimera (PROTAC) compound consist of two parts – one recognizes a specific E3 ligase, and the other recognizes the selected target protein.

Molecular glues, for example, lenalidomide or pomalidomide, have already achieved clinical success and are used to treat cancers such as multiple myeloma. Several PROTAC compounds are currently in advanced clinical trials against breast or prostate cancers, among others. TPD methods make it possible to destroy disease-causing proteins, including oncogenic proteins, and hold great promise for a wide range of therapeutic applications.

Graphic of E2-E3 enzymes' complex where E2 is carrying ubiquitin and E3 is bound to substrate via a PROTAC compound
Molecular glues and PROTACs are two different approaches to targeted protein degradation; molecular glues are small molecules that enhance the interaction between the E3 ligase and the target protein; PROTACs are compounds composed of two components, in which one part recognizes the specific E3 ligase and the other part recognizes the selected target protein. Both approaches result in ubiquitination of the target protein and ultimately lead to its degradation.

Game characters

Meet the awesome characters from the game!
Elementy gry
E3 ubiquitin ligase
Obrazek

The main character of the game. Its goal is to recognize other proteins (substrates) and mediate their ubiquitination which leads to their subsequent destruction.

E2 ubiquitin-conjugating enzyme
Obrazek

The best companion of the E3 ubiquitin ligase. Forms a complex with it and transfers ubiquitin to the target protein.

Substrates

Obrazek

Different proteins, but one goal: tag them with ubiquitin and send for degradation.

Ubiquitin
Obrazek

Gray eminence of the game. Its attachment to the target protein acts as a "destroy me" signal for the proteasome.

Proteasome
Obrazek

Large molecular complex that functions as a cellular recycling center. Recognizes and destroys ubiquitinated proteins.

Deubiquitinating enzyme
Obrazek

Major antagonist. Removes ubiquitin from proteins, preventing their degradation.

Also featuring...

PROTAC
PROTAC (PROteolysis TArgeting Chimera)
Obrazek Our hero, the E3 ubiquitin ligase, can only recognize certain proteins in the cell. However, this is not a problem - thanks to PROTAC compounds, it gains superpowers and can bind entirely new proteins. And guess what? This leads to their ubiquitination and subsequent degradation. So keep calm and degrade on!

For educators

Our game was created with a primary focus on education, as we believe there’s no better way to learn than through having fun. To enrich the journey into the fascinating world of protein degradation, we have prepared a range of downloadable materials to enhance the learning experience and complement the knowledge gained from our game.

Lesson plan (age 15+)

Biology lesson concept for high schools/secondary schools.

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Lesson plan (age 12-15)

Biology lesson concept for the older grades of elementary school.

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Presentation

An editable PowerPoint multimedia presentation for use in a biology lesson.

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Encyclopedia

The Great Encyclopedia of Protein Degradation from the game.

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Quizzes

Quizzes about protein degradation based on the Great Encyclopedia of Protein Degradation.

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Comic

A comic depicting the further adventures of ubiquitin ligase E3 and friends.

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Useful links

Additional educational resources about protein degradation.

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Poster

Promotional poster featuring the game’s logo and its characters.

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Levels description

Detailed description of the game, its characters and each of its levels.

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Authors

Photo of Natalia Szulc
NATALIA
SZULC
Ph.D. student in the laboratory of Dr. Wojciech Pokrzywa at the International Institute of Molecular and Cellular Biology in Warsaw, Poland. Her research focuses on the evolutionary adaptation of proteins to avoid premature degradation, the evolution of degrons and their role in targeted protein degradation methods, and the substrate specificity of ubiquitin ligases - the main inventor and producer of the game.
Photo of Anna Olchowik
ANNA
OLCHOWIK
Skilled game developer with experience in creating advertising games for companies such as PZU and Accuve, educational games for Nova Era publishing house and PGE Group. She actively participated in the eNgage educational project supported by the Foundation for Polish Science. She has published several scientific articles in the field of bioinformatics - the game programmer.
Photo of Patrycja Jaszczak
PATRYCJA JASZCZAK
Visual designer with many years of experience in the mobile game industry. Her main style is vector graphics, which, combined with her knowledge of design, allows creation flexibility while maintaining the graphics’ functionality and quality. In addition to commercial games, she contributes to scientific projects - the creator of all graphics.
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BARTOSZ JANIAK
Sound engineer, composer and multi-instrumentalist. Previously a software engineer, at Google, among others. Currently sharpens his skills at the Academy of Sound Engineering in Warsaw and pursues both of his passions during development of a simulation game for future live audio engineers - author of music, sound design and game trailer.
Photo of Wojciech Pokrzywa
WOJCIECH POKRZYWA
Head of the Protein Metabolism Laboratory at the International Institute of Molecular and Cellular Biology in Warsaw. His team's research focuses on the ubiquitin-proteasome system, the chaperone network, and the role of extracellular vesicles in protein homeostasis, and rare metabolic diseases - the co-inventor and supervisor of the game.

Publication

Available soon!

Acknowledgments

This educational computer game was funded in Poland in part by the Polish State Budget, under the Ministry of Education and Science program entitled the Social Responsibility of Science – grant number SONP/SP/546507/2022; funded amount: 101 706 PLN; total grant value: 115 756 PLN.

Logo of the Social Responsibility of Science funding scheme
Logo of the Polish Ministry of Education and Science

Game partners

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