title: Firefly luciferase mutants as sensors of proteome stress.
abstract: Maintenance of cellular protein homeostasis (proteostasis) depends on a complex network of molecular chaperones, proteases and other regulatory factors. Proteostasis deficiency develops during normal aging and predisposes individuals for many diseases, including neurodegenerative disorders. Here we describe sensor proteins for the comparative measurement of proteostasis capacity in different cell types and model organisms. These sensors are increasingly structurally destabilized versions of firefly luciferase. Imbalances in proteostasis manifest as changes in sensor solubility and luminescence activity. We used EGFP-tagged constructs to monitor the aggregation state of the sensors and the ability of cells to solubilize or degrade the aggregated proteins. A set of three sensor proteins serves as a convenient toolkit to assess the proteostasis status in a wide range of experimental systems, including cell and organism models of stress, neurodegenerative disease and aging.
authors: Department of Cellular Biochemistry, Max Planck Institute of Biochemistry, Martinsried, Germany.
authors: Rajat
authors: R
authors: Gupta
authors: Prasad
authors: P
authors: Kasturi
authors: Andreas
authors: A
authors: Bracher
authors: Christian
authors: C
authors: Loew
authors: Min
authors: M
authors: Zheng
authors: Adriana
authors: A
authors: Villella
authors: Dan
authors: D
authors: Garza
authors: F Ulrich
authors: FU
authors: Hartl
authors: Swasti
authors: S
authors: Raychaudhuri
mesh_terms: D049452:Green Fluorescent Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D006367:HeLa Cells; D006706:Homeostasis; D006801:Humans; D049409:Luciferases, Firefly / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D049449:Luminescence; D008958:Models, Molecular; D050505:Mutant Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D011506:Proteins / Q000378:metabolism*; D020543:Proteome / Q000378:metabolism; D012995:Solubility
chemical_list: D050505:Mutant Proteins; D011506:Proteins; D020543:Proteome; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins; D049409:Luciferases, Firefly