Misfolded proteins are usually ubiquitinated by a tightly controlled E1/E2/E3 ubiquitination cascade and targeted for degradation by the 26S proteasome ( Pickart and Cohen, 2004). The ubiquitin-proteasome system (UPS) is a major eukaryotic proteolytic pathway responsible for the clearance of soluble misfolded proteins. Therefore, different chaperones functionally cooperate with each other, co-chaperones, and other cofactors to promote protein folding, refolding, and degradation. sHsps usually also function as molecular chaperones that typically associate with and hold misfolded proteins in a reversible state through dynamic but ATP-independent oligomerization state changes, which help to facilitate the refolding or degradation of client proteins by other chaperones such as Hsp70 ( Chen et al., 2011). Hsp40 proteins are co-chaperones and essential partners of Hsp70 function with a highly conserved region called the J-domain that can activate the ATPase activity of Hsp70 ( Chen et al., 2011 Hartl et al., 2011). Molecular co-chaperones interact with molecular chaperones to directly influence their ATPase activity and assist them in protein folding and other functions. Molecular chaperones such as Hsp70 and Hsp90 have an ATPase activity and can specifically recognize partially folded or misfolded proteins to promote their folding or other conformational changes in an ATP-dependent manner. In eukaryotic cells, these are chaperones associated with protein synthesis by assisting folding of newly synthesized proteins ( Albanese et al., 2006), heat shock proteins (Hsps), which are generally classified based on their molecular masses (e.g., Hsp100, Hsp90, Hsp70, Hsp60, and Hsp40), and small heat shock proteins (sHsps) ( Hartl et al., 2011). Molecular chaperones also play a critical role in preventing the aggregation and targeting of the degradation of misfolded proteins. In addition, the regulated degradation of native proteins in signaling or other necessities is important to execute regulatory programs in response to specific cellular and environmental cues ( Varshavsky, 2005, 2017).Īll aspects of cellular protein homeostasis rely on molecular chaperones, which promote protein folding, translocation across membrane, and refolding of misfolded or stress-denatured substrates ( Hartl et al., 2011 Tittelmeier et al., 2020). The ability to constantly replenish and adjust a constituent protein pool is not only a vital component for the modulation of responses under stress conditions but also a steady-state feature under normal conditions to maintain cellular homeostasis ( Chen et al., 2011). An elaborate network of protein quality control (PQC) involving molecular chaperones and protein degradation factors and pathways continually monitors, refolds, and degrades misfolded proteins to maintain the integrity of the proteome ( Chen et al., 2011). These misfolded proteins can jeopardize cell viability due to their non-specific interactions with other cellular components and have a tendency to aggregate to form toxic protein inclusions ( Dobson, 2003). In this review, we discuss the structure, cofactors, activities, and biological function of CHIP with an emphasis on both its conserved and unique roles in PQC, stress responses, and signaling in plants.Ī cell is presented with a continuous stream of misfolded proteins as a result of the stochastic fluctuations, and the presence of destabilizing mutations, stress, and other pathological conditions such as cancers and aging ( Hartl and Hayer-Hartl, 2009). CHIP also modulates the activity of protein phosphatase 2A (PP2A), a crucial component in a network of plant signaling, including abscisic acid (ABA) signaling. CHIP protects chloroplasts by coordinating chloroplast PQC both outside and inside the important photosynthetic organelle of plant cells. As a highly conserved ubiquitin ligase, plant CHIP plays an important role in response to a broad spectrum of biotic and abiotic stresses. CHIP also ubiquitinates native proteins and plays a regulatory role in other cellular processes, including signaling, development, DNA repair, immunity, and aging in metazoans. CHIP is a key molecule in PQC by recognizing misfolded proteins through its interacting chaperones and targeting their degradation. A C-terminus of heat shock protein (Hsp) 70-interacting protein is a chaperone-dependent and U-box-containing E3 ligase. Major PQC mechanisms include protein refolding assisted by molecular chaperones and the degradation of misfolded and aggregated proteins using the proteasome and autophagy. Protein quality control (PQC) is essential for maintaining cellular homeostasis by reducing protein misfolding and aggregation. Department of Landscape and Horticulture, Ecology College, Lishui University, Lishui, China.
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