O-GlcNAcylation Determines the Solubility, Filament Organization, and Stability of Keratins 8 and 18*

Budnar, Srikanth; Vaidya, Milind M.; Kalraiya, Rajiv D.

doi:10.1074/jbc.m109.098996

Cited by 68 publications

(67 citation statements)

References 52 publications

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“…Keratin pair 8/18 is widely studied in terms of the regulation of protein interaction, ubiquitination, and filament organization by phosphorylation (52). Keratins 8 and 18 are also highly O-GlcNAcylated (53). OGlcNAcylation increases keratin 8/18 solubility, ubiquitination, and proteasomal degradation.…”

Section: O-glcnacylation Regulates Protein Ubiquitination Via Unknownmentioning

confidence: 99%

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Regulation of Protein Degradation by O-GlcNAcylation: Crosstalk with Ubiquitination

Ruan

Nie

Yang

2013

Molecular & Cellular Proteomics

144

119

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The post-translational modification of intracellular proteins by O-linked N-acetylglucosamine (O-GlcNAc) regulates essential cellular processes such as signal transduction, transcription, translation, and protein degradation. Misfolded, damaged, and unwanted proteins are tagged with a chain of ubiquitin moieties for degradation by the proteasome, which is critical for cellular homeostasis. In this review, we summarize the current knowledge of the interplay between O-GlcNAcylation and ubiquitination in the control of protein degradation. Understanding the mechanisms of action of O-GlcNAcylation in the ubiquitin-proteosome system shall facilitate the development of therapeutics for human diseases such as cancer, metabolic syndrome, and neurodegenerative diseases. Molecular & Cellular

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Section: O-glcnacylation Regulates Protein Ubiquitination Via Unknownmentioning

confidence: 99%

“…There does not seem to be a reciprocal relationship between O-GlcNAcylation and phosphorylation of keratin 8/18 in vivo. The mechanism by which O-GlcNAcylation increases ubiquitination is still a mystery (53).…”

Section: O-glcnacylation Regulates Protein Ubiquitination Via Unknownmentioning

confidence: 99%

Regulation of Protein Degradation by O-GlcNAcylation: Crosstalk with Ubiquitination

Ruan

Nie

Yang

2013

Molecular & Cellular Proteomics

144

119

View full text Add to dashboard Cite

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“…Further investigation is needed to determine the consequences of altered expression of CK18 on cellular function. Investigators have explored various post-translational modifications of CK18, including site-specific phosphorylation (16,19,21), OGlcN-arylation (18,19), and acetylation (20). These modifications regulate each other and determine the solubility, filament organization, and stability of CK8/18.…”

Section: Expression and Clinical Applications Of Ck18 In Cancer Exprementioning

confidence: 99%

Biological Functions of Cytokeratin 18 in Cancer

Weng

Cui²,

Fang³

2012

Molecular Cancer Research

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The structural proteins cytokeratin 18 (CK18) and its coexpressed complementary partner CK8 are expressed in a variety of adult epithelial organs and may play a role in carcinogenesis. In this study, we focused on the biological functions of CK18, which is thought to modulate intracellular signaling and operates in conjunction with various related proteins. CK18 may affect carcinogenesis through several signaling pathways, including the phosphoinositide 3-kinase (PI3K)/Akt, Wnt, and extracellular signal-regulated kinase (ERK) mitogen-activated protein kinase (MAPK) signaling pathways. CK18 acts as an identical target of Akt in the PI3K/Akt pathway and of ERK1/2 in the ERK MAPK pathway, and regulation of CK18 by Wnt is involved in Akt activation. Finally, we discuss the importance of gaining a more complete understanding of the expression of CK18 during carcinogenesis, and suggest potential clinical applications of that understanding. Mol Cancer Res; 10(4); 485-93. Ó2012 AACR.

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“…Although the physiological functions of IF phosphorylation are relatively well established, as mutations of phosphorylation sites can affect filament organization and have pathological effects in cells or animal models, the physiological roles of glycosylation have remained enigmatic. However, new evidence suggests that IF glycosylation can have protective functions for the cell against injury and stress ( Ku et al, 2010), and glycosylation also regulates IF solubility, protein stability and degradation (Srikanth et al, 2010). …”

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confidence: 99%

Insights into intermediate filament regulation from development to ageing

Hyder

Isoniemi

Torvaldson

et al. 2011

Journal of Cell Science

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SummaryIntermediate filament (IF) proteins comprise a large family with more than 70 members. Initially, IFs were assumed to provide only structural reinforcement for the cell. However, IFs are now known to be dynamic structures that are involved in a wide range of cellular processes during all stages of life, from development to ageing, and during homeostasis and stress. This Commentary discusses some lesser-known functional and regulatory aspects of IFs. We specifically address the emerging roles of nestin in myogenesis and cancer cell migration, and examine exciting evidence on the regulation of nestin and lamin A by the notch signalling pathway, which could have repercussions for our understanding of the roles of IF proteins in development and ageing. In addition, we discuss the modulation of the post-translational modifications of neuronally expressed IFs and their protein-protein interactions, as well as IF glycosylation, which not only has a role in stress and ageing, but might also regulate IFs during development. Although many of these recent findings are still preliminary, they nevertheless open new doors to explore the functionality of the IF family of proteins. Journal of Cell ScienceCdk5 is associated with nestin in myoblasts, neuronal precursor cells (Sahlgren et al., 2003) and human podocytes (Bertelli et al., 2007). Cdk5 phosphorylates nestin, and this phosphorylation regulates the organization of nestin filaments (Box 2) during myogenic differentiation (Sahlgren et al., 2003). Interestingly, the interaction between nestin and Cdk5 is not limited to a typical kinase-substrate relationship. In neuronal precursor cells, nestin forms a scaffold for Cdk5 and the Cdk5 activator p35, thereby sequestering them to the cytoplasm, which consequently inhibits the proapoptotic function of Cdk5 during oxidative stress (Sahlgren et al., 2006). In turn, it has recently been demonstrated that Cdk5 is targeted by protein kinase C- (PKC) during myogenesis (de Thonel et al., 2010). PKC is essential for proper myoblast differentiation. It targets Cdk5 by phosphorylating p35 at a site that triggers the activation of calpains, which then cleave p35 into p25. The cleavage of p35 into p25 creates a more stable protein fragment, and this fragment is capable of sustained Cdk5 activation, consequently promoting nestin reorganization (Fig. 1,. An earlier study, in cultured neurons, demonstrated that Cdk5 is also able to regulate p35 by phosphorylation, thereby protecting it from calpain-mediated cleavage (Kamei et al., 2007). Furthermore, a recent study has shown that nestin has the capacity to modulate Cdk5-mediated differentiation and terminal organization of muscle cells (Pallari et al., 2011) (Fig. 1, left-hand side). Taken together, these results suggest that a balance between Cdk5 and PKC is important for proper myogenic differentiation, as they show that disturbance of the PKC-Cdk5-nestin signalling pathway leads to nestin reorganization and impedes myoblast differentiation, implying that nestin also plays a k...

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O-GlcNAcylation Determines the Solubility, Filament Organization, and Stability of Keratins 8 and 18*

Cited by 68 publications

References 52 publications

Regulation of Protein Degradation by O-GlcNAcylation: Crosstalk with Ubiquitination

Regulation of Protein Degradation by O-GlcNAcylation: Crosstalk with Ubiquitination

Biological Functions of Cytokeratin 18 in Cancer

Insights into intermediate filament regulation from development to ageing

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