Abstract
Gene dosage alterations caused by aneuploidy are a common feature of most cancers yet pose severe proteotoxic challenges. Therefore, cells have evolved various dosage compensation mechanisms to limit the damage caused by the ensuing protein level imbalances. For instance, for heteromeric protein complexes, excess nonstoichiometric subunits are rapidly recognized and degraded. In this issue of Genes & Development, Brennan et al. (pp. 1031-1047) reveal that sequestration of nonstoichiometric subunits into aggregates is an alternative mechanism for dosage compensation in aneuploid budding yeast and human cell lines. Using a combination of proteomic and genetic techniques, they found that excess proteins undergo either degradation or aggregation but not both. Which route is preferred depends on the half-life of the protein in question. Given the multitude of diseases linked to either aneuploidy or protein aggregation, this study could serve as a springboard for future studies with broad-spanning implications.
References
Dec 1, 2012·Proceedings of the National Academy of Sciences of the United States of America·Avihu H YonaOrna Dahan
Sep 17, 2013·Nature Cell Biology·Stéphanie Escusa-ToretJudith Frydman
Jan 8, 2014·Disease Models & Mechanisms·Ana B Oromendia, Angelika Amon
Mar 15, 2015·Experimental & Molecular Medicine·Aaron Ciechanover, Yong Tae Kwon
May 23, 2015·Molecular Biology of the Cell·Susanne MuellerRobert Gauss
Oct 1, 2015·ELife·Georges E JanssensMatthias Heinemann
Feb 15, 2016·Trends in Biochemical Sciences·Stuart K Calderwood, Jianlin Gong
Jan 5, 2017·Cold Spring Harbor Perspectives in Medicine·Laurent Sansregret, Charles Swanton
Feb 9, 2017·Scientific Reports·Bani K PathakChandana Barat
May 11, 2017·Annual Review of Biochemistry·Emily Mitchell SontagJudith Frydman
Nov 2, 2017·Nature Communications·Yansheng LiuRuedi Aebersold
Jan 16, 2019·Molecular Systems Biology·Moritz HeuselRuedi Aebersold
Jan 20, 2019·Nature Communications·Aikaterini GeladakiKathryn S Lilley
Mar 8, 2019·ELife·Blake W TyeL Stirling Churchman
Jun 15, 2019·Genes & Development·Christopher M BrennanAngelika Amon
Mar 17, 2019·BioRxiv : the Preprint Server for Biology·E. Kelmer SacramentoAlessandro Ori