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Cellular responses to proteostasis perturbations reveal non-optimal feedback in chaperone networks

Asmita Ghosh, Abhilash Gangadharan, Sarada Das, Monika Verma, Latika Matai, Debasis Dash, Koyeli Mapa, Kausik Chakraborty
doi: https://doi.org/10.1101/137349
Asmita Ghosh
1CSIR-Institute of Genomics and Integrative Biology, Delhi, India 110025
2Academy of Scientific and Innovative Research, Coordination Office, CSIR-Human Resource Development Centre Campus, Ghaziabad, India 201002
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Abhilash Gangadharan
1CSIR-Institute of Genomics and Integrative Biology, Delhi, India 110025
2Academy of Scientific and Innovative Research, Coordination Office, CSIR-Human Resource Development Centre Campus, Ghaziabad, India 201002
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Sarada Das
3Department of Life Sciences, School of Natural Sciences, Shiv Nadar University, Greater Noida, India, 201314
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Monika Verma
1CSIR-Institute of Genomics and Integrative Biology, Delhi, India 110025
2Academy of Scientific and Innovative Research, Coordination Office, CSIR-Human Resource Development Centre Campus, Ghaziabad, India 201002
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Latika Matai
1CSIR-Institute of Genomics and Integrative Biology, Delhi, India 110025
2Academy of Scientific and Innovative Research, Coordination Office, CSIR-Human Resource Development Centre Campus, Ghaziabad, India 201002
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Debasis Dash
1CSIR-Institute of Genomics and Integrative Biology, Delhi, India 110025
2Academy of Scientific and Innovative Research, Coordination Office, CSIR-Human Resource Development Centre Campus, Ghaziabad, India 201002
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Koyeli Mapa
3Department of Life Sciences, School of Natural Sciences, Shiv Nadar University, Greater Noida, India, 201314
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Kausik Chakraborty
1CSIR-Institute of Genomics and Integrative Biology, Delhi, India 110025
2Academy of Scientific and Innovative Research, Coordination Office, CSIR-Human Resource Development Centre Campus, Ghaziabad, India 201002
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  • For correspondence: kausik@igib.in
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Abstract

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.

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Posted August 13, 2018.
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Cellular responses to proteostasis perturbations reveal non-optimal feedback in chaperone networks
Asmita Ghosh, Abhilash Gangadharan, Sarada Das, Monika Verma, Latika Matai, Debasis Dash, Koyeli Mapa, Kausik Chakraborty
bioRxiv 137349; doi: https://doi.org/10.1101/137349
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Cellular responses to proteostasis perturbations reveal non-optimal feedback in chaperone networks
Asmita Ghosh, Abhilash Gangadharan, Sarada Das, Monika Verma, Latika Matai, Debasis Dash, Koyeli Mapa, Kausik Chakraborty
bioRxiv 137349; doi: https://doi.org/10.1101/137349

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