TRIM16 governs the biogenesis and disposal of stress-induced protein aggregates to evade cytotoxicity: implication for neurodegeneration and cancer

Autophagy
Kautilya Kumar JenaSantosh Chauhan

Abstract

The formation of protein aggregates is linked to several diseases collectively called proteinopathies. The mechanisms and the molecular players that control the turnover of protein aggregates are not well defined. We recently showed that TRIM16 acts as a key regulatory protein to control the biogenesis and degradation of protein aggregates. We show that TRIM16 interacts with, enhances K63-linked ubiquitination of, and stabilizes NFE2L2/NRF2 leading to its activation. The activated NFE2L2 upregulates the SQSTM1/p62 and ubiquitin pathway proteins, which interact with and ubiquitinate the misfolded proteins resulting in protein aggregate formation. TRIM16 is physically present around the protein aggregates and acts as a scaffold protein to recruit SQSTM1 and macroautophagy/autophagy initiation proteins for sequestration of the protein aggregates within autophagosomes, leading to their degradation. Hence, TRIM16 utilizes a two-pronged approach to safely dispose of the stress-induced misfolded proteins and protein aggregates, and protect cells from oxidative and proteotoxic stresses. This study could provide a framework for understanding the mechanisms of protein aggregate formation in neurodegeneration. The enhancement of TRIM16 ac...Continue Reading

References


❮ Previous
Next ❯

Citations

Sep 29, 2020·Frontiers in Cell and Developmental Biology·Litian ZhangLiang Chen
Aug 28, 2020·Cancers·Claudio Brancolini, Luca Iuliano
Jul 25, 2020·Journal of Hematology & Oncology·Chaeuk ChungEun-Kyeong Jo
May 21, 2021·Oxidative Medicine and Cellular Longevity·Chao Yu, Jian-Hui Xiao

❮ Previous
Next ❯

Methods Mentioned

BETA
ubiquitination
xenograft

Related Concepts

Related Feeds

Autophagy & Aging: Inhibitors

The feed focuses on the role of nuclear export inhibitors and their effect on autophagy and the aging process.

Autophagy & Disease

Autophagy is an important cellular process for normal physiology and both elevated and decreased levels of autophagy are associated with disease. Here is the latest research.

Parkinson's Disease & Autophagy (MDS)

Autophagy leads to degradation of damaged proteins and organelles by the lysosome. Impaired autophagy has been implicated in several diseases. Here is the role of autophagy in Parkinson’s disease.

Autophagosome

An autophagosome is the formation of double-membrane vesicles that involve numerous proteins and cytoplasmic components. These double-membrane vesicles are then terminated at the lysosome where they are degraded. Discover the latest research on autophagosomes here.

Autophagy & Metabolism

Autophagy preserves the health of cells and tissues by replacing outdated and damaged cellular components with fresh ones. In starvation, it provides an internal source of nutrients for energy generation and, thus, survival. A powerful promoter of metabolic homeostasis at both the cellular and whole-animal level, autophagy prevents degenerative diseases. It does have a downside, however--cancer cells exploit it to survive in nutrient-poor tumors.

Autophagy & Model Organisms

Autophagy is a cellular process that allows degradation by the lysosome of cytoplasmic components such as proteins or organelles. Here is the latest research on autophagy & model organisms

Autophagy Networks

Autophagy is a lysosomal pathway that involves degradation of proteins and functions in normal growth and pathological conditions, through a series of complex networks. The catabolic process involves delivery of proteins and organelles to the lysosome. Here is the latest research on autophagy networks.

Autophagosome

An autophagosome is the formation of double-membrane vesicles that involve numerous proteins and cytoplasmic components. These double-membrane vesicles are then terminated at the lysosome where they are degraded. Discover the latest research on autophagosomes here.