Volume 1510, Issue 1 p. 79-99
CONCISE ORIGINAL REPORT

Targeted protein degradation: from small molecules to complex organelles—a Keystone Symposia report

Jennifer Cable

Corresponding Author

Jennifer Cable

PhD Science Writer, New York, New York

Address for correspondence: [email protected]

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Eilika Weber-Ban

Eilika Weber-Ban

Institute of Molecular Biology and Biophysics, ETH Zurich, Zurich, Switzerland

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Tim Clausen

Tim Clausen

Research Institute of Molecular Pathology (IMP), Vienna BioCenter and Medical University of Vienna, Vienna, Austria

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Kylie J. Walters

Kylie J. Walters

Protein Processing Section, Center for Structural Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, Maryland

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Michal Sharon

Michal Sharon

Department of Bimolecular Sciences, Weizmann Institute of Science, Rehovot, Israel

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Daniel J. Finley

Daniel J. Finley

Department of Cell Biology, Harvard Medical School, Boston, Massachusetts

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Yangnan Gu

Yangnan Gu

Department of Plant and Microbial Biology and Innovative Genomics Institute, University of California, Berkeley, California

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John Hanna

John Hanna

Department of Pathology, Harvard Medical School and Brigham and Women's Hospital, Boston, Massachusetts

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Yue Feng

Yue Feng

Princess Margaret Cancer Centre, University Health Network and Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada

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Sascha Martens

Sascha Martens

Max Perutz Labs, University of Vienna, Vienna BioCenter (VBC), Vienna, Austria

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Anne Simonsen

Anne Simonsen

Department of Molecular Medicine, Institute of Basic Medical Sciences and Centre for Cancer Cell Reprogramming, Institute of Clinical Medicine, University of Oslo, Oslo, Norway

Department of Molecular Cell Biology, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway

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Malene Hansen

Malene Hansen

Sanford Burnham Prebys Medical Discovery Institute, Program of Development, Aging, and Regeneration, La Jolla, California

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Hong Zhang

Hong Zhang

National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences and College of Life Sciences, University of Chinese Academy of Sciences, Beijing, People's Republic of China

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Jonathan M. Goodwin

Jonathan M. Goodwin

Casma Therapeutics, Cambridge, Massachusetts

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Alessio Reggio

Alessio Reggio

Telethon Institute of Genetics and Medicine (TIGEM), Pozzuoli, Italy

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Chunmei Chang

Chunmei Chang

Molecular and Cell Biology, University of California, Berkeley, Berkeley, California

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Liang Ge

Liang Ge

State Key Laboratory of Membrane Biology, Tsinghua University-Peking University Joint Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing, China

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Brenda A. Schulman

Brenda A. Schulman

Department of Molecular Machines and Signaling, Max Planck Institute of Biochemistry, Martinsried, Germany

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Raymond J. Deshaies

Raymond J. Deshaies

Amgen, Inc., Thousand Oaks, California

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Ivan Dikic

Ivan Dikic

Institute of Biochemistry II, School of Medicine and Buchmann Institute for Molecular Life Sciences, Goethe University, Frankfurt, Germany

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J. Wade Harper

J. Wade Harper

Department of Cell Biology, Blavatnik Institute, Harvard Medical School, Boston, Massachusetts

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Ingrid E. Wertz

Ingrid E. Wertz

Departments of Molecular Oncology and Early Discovery Biochemistry, Genentech, Inc., South San Francisco, California

Bristol Myers Squibb, Brisbane, California

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Nicolas H. Thomä

Nicolas H. Thomä

Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland

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Mikołaj Słabicki

Mikołaj Słabicki

Broad Institute of MIT and Harvard, Cambridge, Massachusetts

Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts

Division of Translational Medical Oncology, German Cancer Research Center (DKFZ) and National Center for Tumor Diseases (NCT), Heidelberg, Germany

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Judith Frydman

Judith Frydman

Biophysics Graduate Program, Department of Biology and Department of Genetics, Stanford University, Stanford, California

Biohub, San Francisco, California

Division of CryoEM and Bioimaging, SSRL, SLAC National Accelerator Laboratory, Menlo Park, California

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Ursula Jakob

Ursula Jakob

Department of Molecular, Cellular and Developmental Biology, College of Literature, Science, and the Arts, University of Michigan, Ann Arbor, Michigan

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Della C. David

Della C. David

German Center for Neurodegenerative Diseases (DZNE), and Interfaculty Institute of Biochemistry, University of Tübingen, Tübingen, Germany

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Eric J. Bennett

Eric J. Bennett

Section of Cell and Developmental Biology, Division of Biological Sciences, University of California, San Diego, La Jolla, California

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Carolyn R. Bertozzi

Carolyn R. Bertozzi

Department of Chemistry and Stanford ChEM-H, Stanford University and Howard Hughes Medical Institute, Stanford, California

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Richa Sardana

Richa Sardana

Weill Institute of Cell and Molecular Biology and Department of Molecular Biology and Genetics, Cornell University, Ithaca, New York

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Vinay V. Eapen

Vinay V. Eapen

Department of Cell Biology, Harvard Medical School, Boston, Massachusetts

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Serena Carra

Serena Carra

Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Modena, Italy

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First published: 08 January 2022
Citations: 3

Abstract

Targeted protein degradation is critical for proper cellular function and development. Protein degradation pathways, such as the ubiquitin proteasomes system, autophagy, and endosome–lysosome pathway, must be tightly regulated to ensure proper elimination of misfolded and aggregated proteins and regulate changing protein levels during cellular differentiation, while ensuring that normal proteins remain unscathed. Protein degradation pathways have also garnered interest as a means to selectively eliminate target proteins that may be difficult to inhibit via other mechanisms. On June 7 and 8, 2021, several experts in protein degradation pathways met virtually for the Keystone eSymposium “Targeting protein degradation: from small molecules to complex organelles.” The event brought together researchers working in different protein degradation pathways in an effort to begin to develop a holistic, integrated vision of protein degradation that incorporates all the major pathways to understand how changes in them can lead to disease pathology and, alternatively, how they can be leveraged for novel therapeutics.