Shaping proteostasis at the cellular, tissue, and organismal level.
TLDR
This review by Morimoto and colleagues examines mechanisms by which protein homeostasis (proteostasis) is achieved in multicellular organisms and discusses the implications for health and disease.Abstract:
The proteostasis network (PN) regulates protein synthesis, folding, transport, and degradation to maintain proteome integrity and limit the accumulation of protein aggregates, a hallmark of aging and degenerative diseases. In multicellular organisms, the PN is regulated at the cellular, tissue, and systemic level to ensure organismal health and longevity. Here we review these three layers of PN regulation and examine how they collectively maintain cellular homeostasis, achieve cell type-specific proteomes, and coordinate proteostasis across tissues. A precise understanding of these layers of control has important implications for organismal health and could offer new therapeutic approaches for neurodegenerative diseases and other chronic disorders related to PN dysfunction.read more
Citations
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HSF1 Drives a Transcriptional Program Distinct from Heat Shock to Support Highly Malignant Human Cancers
Marc L. Mendillo,Sandro Santagata,George W. Bell,Rong Hu,Rulla M. Tamimi,Ernest Fraenkel,Tan A. Ince,Luke Whitesell,Susan Lindquist,Martina Koeva +9 more
TL;DR: This work identifies an HSF1-regulated transcriptional program specific to highly malignant cells and distinct from heat shock, active in breast, colon and lung tumors isolated directly from human patients and strongly associated with metastasis and death.
Journal ArticleDOI
Emerging New Concepts of Degrader Technologies.
Yu Ding,Yiyan Fei,Boxun Lu +2 more
TL;DR: In this article, the authors review key emerging technologies that exploit the lysosomal degradation pathway and discuss their potential applications and limitations, as well as emerging new degrader technologies may greatly broaden the spectrum of targets that could be selectively degraded by harnessing a second major degradation pathway in cells.
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Chaperoning Endoplasmic Reticulum-Associated Degradation (ERAD) and Protein Conformational Diseases.
TL;DR: The factors that constitute the ERAD machinery are discussed and detail how each step in the pathway occurs, and the underlying pathophysiology of protein conformational diseases associated with ERAD is highlighted.
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Proteasome storage granules protect proteasomes from autophagic degradation upon carbon starvation.
TL;DR: PSG formation and concomitant protection against proteaphagy also occurs in Arabidopsis, suggesting that PSGs represent an evolutionarily conserved cache of proteasomes that can be rapidly re-mobilized based on energy availability.
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Integrating the DNA damage and protein stress responses during cancer development and treatment.
Vassilis G. Gorgoulis,Vassilis G. Gorgoulis,Vassilis G. Gorgoulis,Dafni-Eleftheria Pefani,Ioannis S. Pateras,Ioannis P. Trougakos +5 more
TL;DR: The role of oncogene‐induced DNA damage as a driving force that shapes the cellular landscape for the emergence of the various hallmarks of cancer is emphasized and potential means to exploit key cancer‐related alterations of the genome and proteome damage response pathways are discussed in order to develop novel efficient therapeutic modalities.
References
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Mathias Uhlén,Mathias Uhlén,Linn Fagerberg,Björn M. Hallström,Cecilia Lindskog,Per Oksvold,Adil Mardinoglu,Åsa Sivertsson,Caroline Kampf,Evelina Sjöstedt,Evelina Sjöstedt,Anna Asplund,IngMarie Olsson,Karolina Edlund,Emma Lundberg,Sanjay Navani,Cristina Al-Khalili Szigyarto,Jacob Odeberg,Dijana Djureinovic,Jenny Ottosson Takanen,Sophia Hober,Tove Alm,Per-Henrik Edqvist,Holger Berling,Hanna Tegel,Jan Mulder,Johan Rockberg,Peter Nilsson,Jochen M. Schwenk,Marica Hamsten,Kalle von Feilitzen,Mattias Forsberg,Lukas Persson,Fredric Johansson,Martin Zwahlen,Gunnar von Heijne,Jens Nielsen,Jens Nielsen,Fredrik Pontén +38 more
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The Ubiquitin System
Avram Hershko,Aaron Ciechanover +1 more
TL;DR: This review discusses recent information on functions and mechanisms of the ubiquitin system and focuses on what the authors know, and would like to know, about the mode of action of ubi...
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The Unfolded Protein Response: From Stress Pathway to Homeostatic Regulation
Peter Walter,David Ron +1 more
TL;DR: The vast majority of proteins that a cell secretes or displays on its surface first enter the endoplasmic reticulum, where they fold and assemble, and only properly assembled proteins advance from the ER to the cell surface.
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An nrf2/small maf heterodimer mediates the induction of phase ii detoxifying enzyme genes through antioxidant response elements
Ken Itoh,Tomoki Chiba,Satoru Takahashi,Tetsuro Ishii,Kazuhiko Igarashi,Yasutake Katoh,Tatsuya Oyake,Norio Hayashi,Kimihiko Satoh,Ichiro Hatayama,Masayuki Yamamoto,Yo-ichi Nabeshima +11 more
TL;DR: It is demonstrated that Nrf2 is essential for the transcriptional induction of phase II enzymes and the presence of a coordinate transcriptional regulatory mechanism for phase II enzyme genes and the nrf2-deficient mice may prove to be a very useful model for the in vivo analysis of chemical carcinogenesis and resistance to anti-cancer drugs.
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Identification of Ubiquitin Ligases Required for Skeletal Muscle Atrophy
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TL;DR: Two genes encode ubiquitin ligases that are potential drug targets for the treatment of muscle atrophy, and mice deficient in either MAFbx orMuRF1 were found to be resistant to atrophy.