Dataset Information

Identification of Proteins Sensitive to Thermal Stress in Human HEK293 cells

ABSTRACT: Heat-shock is an acute insult to the mammalian proteome. The sudden elevation in temperature has far-reaching effects on protein metabolism, leads to a rapid inhibition of most protein synthesis, and the induction of protein chaperones. Using heat-shock in human HEK293 cells, in conjunction with detergent extraction and sedimentation followed by LC-MS/MS proteomic approaches, we identify proteins that lose solubility upon heat-shock. We assume that these are metastable in protein homeostasis.

INSTRUMENT(S): QSTAR

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Cell Culture, Early Embryonic Cell

DISEASE(S): Disease Free

SUBMITTER: Guilian Xu

LAB HEAD: David R. Borchelt

PROVIDER: PXD003888 | Pride | 2016-04-11

REPOSITORIES: Pride

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Publications

Vulnerability of newly synthesized proteins to proteostasis stress.

Xu Guilian G Pattamatta Amrutha A Hildago Ryan R Pace Michael C MC Brown Hilda H Borchelt David R DR

Journal of cell science 20160329 9

The capacity of the cell to produce, fold and degrade proteins relies on components of the proteostasis network. Multiple types of insults can impose a burden on this network, causing protein misfolding. Using thermal stress, a classic example of acute proteostatic stress, we demonstrate that ∼5-10% of the soluble cytosolic and nuclear proteome in human HEK293 cells is vulnerable to misfolding when proteostatic function is overwhelmed. Inhibiting new protein synthesis for 30 min prior to heat-sh ...[more]

PMID: 27026526

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Project description:Proctor2005 - Actions of chaperones and their role in ageing This model is described in the article: Modelling the actions of chaperones and their role in ageing. Proctor CJ, Soti C, Boys RJ, Gillespie CS, Shanley DP, Wilkinson DJ, Kirkwood TB. Mech. Ageing Dev. 2005 Jan; 126(1): 119-131 Abstract: Many molecular chaperones are also known as heat shock proteins because they are synthesised in increased amounts after brief exposure of cells to elevated temperatures. They have many cellular functions and are involved in the folding of nascent proteins, the re-folding of denatured proteins, the prevention of protein aggregation, and assisting the targeting of proteins for degradation by the proteasome and lysosomes. They also have a role in apoptosis and are involved in modulating signals for immune and inflammatory responses. Stress-induced transcription of heat shock proteins requires the activation of heat shock factor (HSF). Under normal conditions, HSF is bound to heat shock proteins resulting in feedback repression. During stress, cellular proteins undergo denaturation and sequester heat shock proteins bound to HSF, which is then able to become transcriptionally active. The induction of heat shock proteins is impaired with age and there is also a decline in chaperone function. Aberrant/damaged proteins accumulate with age and are implicated in several important age-related conditions (e.g. Alzheimer's disease, Parkinson's disease, and cataract). Therefore, the balance between damaged proteins and available free chaperones may be greatly disturbed during ageing. We have developed a mathematical model to describe the heat shock system. The aim of the model is two-fold: to explore the heat shock system and its implications in ageing; and to demonstrate how to build a model of a biological system using our simulation system (biology of ageing e-science integration and simulation (BASIS)). This model is hosted on BioModels Database and identified by: BIOMD0000000091. To cite BioModels Database, please use: BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models. To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication for more information.

Dataset Information

Identification of Proteins Sensitive to Thermal Stress in Human HEK293 cells

Publications

Vulnerability of newly synthesized proteins to proteostasis stress.

Similar Datasets

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