PMID: 20356926

 

    Legend: Gene, Sites

Title : N-linked glycosylation is required for optimal proteolytic activation of membrane-bound transcription factor CREB-H

Abstract :

1. CREB-H is a liver-enriched bZIP transcription factor of the CREB3 subfamily
2. CREB-H is activated by intramembrane proteolysis that removes a C-terminal transmembrane domain
3. Aberrant expression of CREB-H is implicated in liver cancer
4. In this study we characterized N-linked glycosylation of CREB-H in the luminal domain at the C-terminus
5. We found that CREB-H is modified at three N-linked glycosylation sites in this region
6. Disruption of all three sites by site-directed mutagenesis completely abrogated N-linked glycosylation of CREB-H
7. The unglycosylated mutant of CREB-H was not unstable, unfolded or aggregated
8. Upon stimulation with an activator of intramembrane proteolysis such as brefeldin A and KDEL-tailed site 1 protease , unglycosylated or deglycosylated CREB-H was largely uncleaved, retained in an inactive form in the endoplasmic reticulum, and less capable of activating transcription driven by unfolded protein response element or C-reactive protein promoter
9. Taken together, our findings suggest that N-linked glycosylation is required for full activation of CREB-H through intramembrane proteolysis
10. Our work also reveals a novel mechanism for the regulation of CREB-H-dependent transcription

Output (sent_index, trigger, protein, sugar, site):

• 0. glycosylation, , factor, -, -
• 4. glycosylation, , -, -, domain
• 4. glycosylation, , CREB-H, -, domain
• 5. glycosylation, , -, -, sites
• 6. glycosylation, , CREB-H, -, -
• 8. deglycosylated, , CREB-H, -, -
• 8. unglycosylated, , CREB-H, -, -
• 9. glycosylation, , CREB-H, -, -

Output(Part-Of) (sent_index, protein, site):

*Output_Site_Fusion* (sent_index, protein, sugar, site):

 

Protein	NCBI ID	SENTENCE INDEX
C-reactive protein	1401	8
CREB-H	84699	0,1,2,3,4,5,6,7,8,9,10
CREB3	10488	1