TRIM16 employs NRF2, ubiquitin system and aggrephagy for safe disposal of stress-induced misfolded proteins
Authors:Kautilya Kumar Jena1,2, Subhash Mehto1, Srinivasa Prasad Kolapalli1, Parej Nath1, Swati Chauhan1 and Santosh Chauhan1
1 Cell Biology and Infectious Diseases Unit, Institute of Life Sciences, Bhubaneswar, 751023, India.
2 School of Biotechnology, KIIT University, Bhubaneswar, 751023, India.
Keywords:
TRIM16, NRF2/NFE2L2, p62/SQSTM1, autophagy, protein aggregates, cancer, oxidative stress, protein homeostasis, protein quality control, aggrephagy, proteotoxic stress.
Corresponding Author(s):
Conflict of interest statement:
The authors declare that they have no conflict of interests.
Please cite this article as:
Kautilya Kumar Jena, Subhash Mehto, Srinivasa Prasad Kolapalli, Parej Nath, Swati Chauhan and Santosh Chauhan (2018). TRIM16 employs NRF2, ubiquitin system and aggrephagy for safe disposal of stress-induced misfolded proteins. Cell Stress 2(12): 365-367. doi: 10.15698/cst2018.12.169
© 2018 Jena et al. This is an open-access article released under the terms of the Creative Commons Attribution (CC BY) license, which allows the unrestricted use, distribution, and reproduction in any medium, provided the original author and source are acknowledged.
Abstract:
The cellular stresses, genetic mutations, and environmental factors can critically affect the protein quality control checkpoints resulting in protein misfolding. Molecular chaperones play a crucial role in maintaining the healthy proteome by refolding the misfolded proteins into the native functional conformations. However, if they fail to refold the misfolded proteins into the native state, they are targeted by proteolytic systems for degradation. If the misfolded protein numbers increase more than what a cell can resolve, they get converted protein aggregates/inclusion bodies. The inclusion bodies are less cytotoxic than misfolded proteins. The enhanced production of misfolded proteins and protein aggregates are linked to several diseases collectively termed proteinopathies, which includes several neurodegenerative disorders. The understanding of molecular mechanisms that regulate the turnover of protein aggregates will pave path for therapeutic interventions of proteinopathies. In a recent report, we showed that a tripartite motif (TRIM) family protein, TRIM16 streamlines the process of protein aggregates turnover by regulating the NRF2-p62 axis and autophagy.