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

Cable, Jennifer; Weber‐Ban, Eilika; Clausen, Tim; Walters, Kylie J.; Sharon, Michal; Finley, Daniel J.; Gu, Yangnan; Hanna, John; Feng, Yue; Martens, Sascha; Simonsen, Anne; Hansen, Malene; Zhang, Hong; Goodwin, Jonathan M.; Reggio, Alessio; Chang, Chunmei; Ge, Liang; Schulman, Brenda A.; Deshaies, Raymond J.; Dikic, Ivan; Harper, J. Wade; Wertz, Ingrid E.; Thomä, Nicolas H.; Słabicki, Mikołaj; Frydman, Judith; Jakob, Ursula; David, Della C.; Bennett, Eric J.; Bertozzi, Carolyn R.; Sardana, Richa; Eapen, Vinay V.; Carra, Serena

doi:10.1111/nyas.14745

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

Journal Article · 07 January 2022 · Annals of the New York Academy of Sciences

DOI: https://doi.org/10.1111/nyas.14745 · OSTI ID:1863764

Cable, Jennifer ^[1]; Weber‐Ban, Eilika ^[2]; Clausen, Tim ^[3]; Walters, Kylie J. ^[4]; Sharon, Michal ^[5]; Finley, Daniel J. ^[6]; Gu, Yangnan ^[7]; Hanna, John ^[8]; Feng, Yue ^[9]; Martens, Sascha ^[10]; Simonsen, Anne ^[11]; Hansen, Malene ^[12]; Zhang, Hong ^[13]; Goodwin, Jonathan M. ^[14]; Reggio, Alessio ^[15]; Chang, Chunmei ^[16]; Ge, Liang ^[17]; Schulman, Brenda A. ^[18]; Deshaies, Raymond J. ^[19]; Dikic, Ivan ^[20] more »

PhD Science Writer, New York, NY (United States)
ETH Zurich (Switzerland). Inst. of Molecular Biology and Biophysics
Vienna BioCenter and Medical University of Vienna (Austria). Research Institute of Molecular Pathology (IMP)
National Institutes of Health (NIH), Frederick MD (United States). National Cancer Inst., Center for Cancer Research, Center for Structural Biology
Weizmann Institute of Science, Rehovot (Israel)
Harvard Medical School, Boston, MA (United States)
Univ. of California, Berkeley, CA (United States). Innovative Genomics Inst.
Brigham and Women's Hospital (Harvard Medical School), Boston, MA (United States)
Univ. of Toronto, ON (Canada). Princess Margaret Cancer Centre
Univ. of Vienna (Austria). Vienna BioCenter (VBC), Max Perutz Labs
Univ. of Oslo (Norway). Institute of Basic Medical Sciences, Centre for Cancer Cell Reprogramming, Institute of Clinical Medicine; Oslo Univ. Hospital (Norway). Institute for Cancer Research
Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA (United States)
Chinese Academy of Sciences (CAS), Beijing (China). Inst. of Biophysics, CAS Center for Excellence in Biomacromolecules, National Laboratory of Biomacromolecules; University of Chinese Academy of Sciences, Beijing (China)
Casma Therapeutics, Cambridge, MA (United States)
Telethon Institute of Genetics and Medicine (TIGEM), Pozzuoli (Italy)
Univ. of California, Berkeley, CA (United States)
Tsinghua Univ., Beijing (China); Tsinghua Univ.-Peking Univ. Joint Center for Life Sciences, Beijing (China). State Key Laboratory of Membrane Biology
Max Planck Institute of Biochemistry, Martinsried (Germany)
Amgen, Inc., Thousand Oaks, CA (United States)
Goethe Univ., Frankfurt (Germany). Institute of Biochemistry, Buchmann Institute for Molecular Life Sciences
Harvard Medical School, Boston, MA (United States). Blavatnik Inst.
Genentech, Inc., South San Francisco, CA (United States); Bristol Myers Squibb, Brisbane, CA (United States)
Friedrich Miescher Institute for Biomedical Research, Basel (Switzerland)
Broad Institute of MIT and Harvard, Cambridge, MA (United States); Dana‐Farber Cancer Institute, Boston, MA (United States); German Cancer Research Center (DKFZ), Heidelberg (Germany); National Center for Tumor Diseases (NCT), Heidelberg (Germany)
Biohub, San Francisco, CA (United States); Stanford Univ., CA (United States); SLAC National Accelerator Lab., Menlo Park, CA (United States). Stanford Synchrotron Radiation Lightsource (SSRL)
Univ. of Michigan, Ann Arbor, MI (United States)
University of Tübingen (Germany). Interfaculty Institute of Biochemistry, German Center for Neurodegenerative Diseases (DZNE)
Univ. of California San Diego, La Jolla, CA (United States)
Howard Hughes Medical Inst., Stanford, CA (United States); Stanford Univ., CA (United States)
Cornell Univ., Ithaca, NY (United States). Weill Institute of Cell and Molecular Biology
University of Modena and Reggio Emilia (Italy)

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. Additionally, 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.

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Research Organization:: SLAC National Accelerator Laboratory (SLAC), Menlo Park, CA (United States)

Sponsoring Organization:: USDOE Office of Science (SC), Basic Energy Sciences (BES)

Grant/Contract Number:: AC02-76SF00515

OSTI ID:: 1863764

Journal Information:: Annals of the New York Academy of Sciences, Journal Name: Annals of the New York Academy of Sciences Journal Issue: 1 Vol. 1510; ISSN 0077-8923

Publisher:: WileyCopyright Statement

Country of Publication:: United States

Language:: English

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