RT Journal Article
SR Electronic
T1 Cellular responses to proteostasis perturbations reveal non-optimal feedback in chaperone networks
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 137349
DO 10.1101/137349
A1 Asmita Ghosh
A1 Abhilash Gangadharan
A1 Sarada Das
A1 Monika Verma
A1 Latika Matai
A1 Debasis Dash
A1 Koyeli Mapa
A1 Kausik Chakraborty
YR 2018
UL http://biorxiv.org/content/early/2018/08/13/137349.abstract
AB The proteostasis network (PN) comprises a plethora of proteins that are dedicated to aid in protein folding; some with over-lapping functions. Despite this, there are multiple pathophysiological states associated with depletion of chaperones. This is counter-intuitive assuming cells have the ability to re-program transcriptional outputs in accordance with its proteostasic limitations. To this effect, we have used S. cerevisiae to understand the route a cell takes as a response when challenged with different proteostasis impairments. Using 14 single deletion strains of genes of Protein Quality Control (PQC) system, we quantify their proteostasis impairment and the transcriptional response. In most cases cellular response was incapable of restoring proteostasis. The response did not activate proteostasis components or pathways that could complement the function of the missing PQC gene. Over-expression of alternate machineries, could restore part of the proteostasis defect in deletion strains. We posit that epistasis guided synthetic biology approaches may be helpful in realizing the true potential of the cellular chaperone machinery.