O-GlcNAcylation determines the solubility, filament organization, and stability of keratins 8 and 18

Srikanth, Budnar, Vaidya, Milind M. and Kalraiya, Rajiv D. (2010) O-GlcNAcylation determines the solubility, filament organization, and stability of keratins 8 and 18. Journal of Biological Chemistry, 285 44: 34062-34071. doi:10.1074/jbc.M109.098996

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Author Srikanth, Budnar
Vaidya, Milind M.
Kalraiya, Rajiv D.
Title O-GlcNAcylation determines the solubility, filament organization, and stability of keratins 8 and 18
Journal name Journal of Biological Chemistry   Check publisher's open access policy
ISSN 0021-9258
Publication date 2010-10
Sub-type Article (original research)
DOI 10.1074/jbc.M109.098996
Open Access Status File (Publisher version)
Volume 285
Issue 44
Start page 34062
End page 34071
Total pages 10
Place of publication Bethesda, MD, United States
Publisher American Society for Biochemistry and Molecular Biology
Language eng
Abstract Keratins 8 and 18 (K8/18) are intermediate filament proteins expressed specifically in simple epithelial tissues. Dynamic equilibrium of these phosphoglycoproteins in the soluble and filament pool is an important determinant of their cellular functions, and it is known to be regulated by site-specific phosphorylation. However, little is known about the role of dynamic O-GlcNAcylation on this keratin pair. Here, by comparing immortalized (Chang) and transformed hepatocyte (HepG2) cell lines, we have demonstrated that O-GlcNAcylation of K8/18 exhibits a positive correlation with their solubility (Nonidet P-40 extractability). Heat stress, which increases K8/18 solubility, resulted in a simultaneous increase in O-GlcNAc on these proteins. Conversely, increasing O-GlcNAc levels were associated with a concurrent increase in their solubility. This was also associated with a notable decrease in total cellular levels of K8/18. Unaltered levels of transcripts and the reduced half-life of K8 and K18 indicated their decreased stability on increasing O-GlcNAcylation. On the contrary, the K18 glycosylation mutant (K18 S29A/S30A/S48A) was notably more stable than the wild type K18 in Chang cells. The K18-O-GlcNAc mutant accumulated as aggregates upon stable expression, which possibly altered endogenous filament architecture. These results strongly indicate the involvement of O-GlcNAc on K8/18 in regulating their solubility and stability, which may have a bearing on the functions of these keratins.
Keyword Simple epithelial keratins
Cellular functions
Heat stress
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: Institute for Molecular Bioscience - Publications
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Citation counts: TR Web of Science Citation Count  Cited 28 times in Thomson Reuters Web of Science Article | Citations
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Created: Fri, 09 Nov 2012, 12:49:25 EST by Susan Allen on behalf of Institute for Molecular Bioscience