Cellular Strategies to Combat Protein Misfolding: Intricate Role of Hsp70 in Stress Management

Author(s): Joydeep Roy, Atin K. Mandal

Journal Name: Current Chemical Biology

Volume 8 , Issue 3 , 2014

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Abstract:

Proteins are always at risk inside the cellular environment. Stress enhances the propensity of protein misfolding. Cell has evolved dynamic machinery called protein quality control (PQC) to minimize the risk of protein misfolding. The efficiency of PQC decreases during ageing; and the tendency of misfolded protein accumulation reduces the lifespan of an organism. Cell reduces the flux of misfolded proteins by refolding, degradation, or by sequestering into inclusions. Several evidences support the involvement of molecular chaperones that act as primary cellular defense. Among these, Hsp70 protein plays the prime function in maintaining PQC. Hsp70 has the unique ability to attune its function in response to the cellular need. From folding to degradation, solubilising aggregates, refolding of damaged proteins, and preventing harmful assemblage of protein inclusions, Hsp70 portrays a wide array of functions. These functions are attributed by the chaperone alone or along with its co-chaperones, Hsp40 (J-proteins), Hsp110 (NEF’s) or Hsp104. Recent studies indicate Hsp70 as a degradation chaperone that efficiently facilitates in clearance of misfolded proteins. We discuss here the diverse roles of Heat Shock Protein 70 (Hsp70) chaperone in client fate determination. Moreover, we focus on the strategies cell undertake when major chaperone functions are compromised due to targeted inhibition or particular stress conditions. In the light of these findings, we discuss how chaperone modulation can evolve as an effective strategy to combat various neuropathies, ion channel misfolding diseases and selective parasitic maladies.

Keywords: Chaperone, degradation, HSP70, protein quality control.

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Article Details

VOLUME: 8
ISSUE: 3
Year: 2014
Page: [149 - 164]
Pages: 16
DOI: 10.2174/221279680803150420094608
Price: $25

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