Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UMLS:C0345904 (
liver cancer
)
15,188
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
CREB-H
is a liver-enriched bZIP transcription factor of the CREB3 subfamily.
CREB-H
is activated by intramembrane proteolysis that removes a C-terminal transmembrane domain. Aberrant expression of
CREB-H
is implicated in
liver cancer
. In this study we characterized N-linked glycosylation of
CREB-H
in the luminal domain at the C-terminus. We found that
CREB-H
is modified at three N-linked glycosylation sites in this region. Disruption of all three sites by site-directed mutagenesis completely abrogated N-linked glycosylation of
CREB-H
. The unglycosylated mutant of
CREB-H
was not unstable, unfolded or aggregated. 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. Taken together, our findings suggest that N-linked glycosylation is required for full activation of
CREB-H
through intramembrane proteolysis. Our work also reveals a novel mechanism for the regulation of
CREB-H
-dependent transcription.
...
PMID:N-linked glycosylation is required for optimal proteolytic activation of membrane-bound transcription factor CREB-H. 2035 26
