Title : O-GlcNAcylation determines the solubility, filament organization, and stability of
keratins 8 and 18
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
Output (sent_index, trigger,
protein,
sugar,
site):
- 2. phosphoglycoproteins, , phosphoglycoproteins, an important determinant, -
- 4. K8/18, , K8/18, O-GlcNAcylation, -
Output(Part-Of) (sent_index,
protein,
site):
*Output_Site_Fusion* (sent_index,
protein,
sugar,
site):