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)
Fumarylacetoacetate hydrolase
(
FAH
) is the last enzyme in the degradation pathway of the amino acids tyrosine and phenylalanine in mammals that catalyzes the hydrolysis of 4-fumarylacetoacetate into acetoacetate and fumarate. Mutations of the
FAH
gene are associated with hereditary tyrosinemia type I (HT1), resulting in reduced protein stability, misfolding, accelerated degradation and deficiency in functional proteins. Identifying E3 ligases, which are necessary for
FAH
protein stability and degradation, is essential. In this study, we demonstrated that the
FAH
protein level is elevated in
liver cancer
tissues compared to that in normal tissues. Further, we showed that the
FAH
protein undergoes 26S proteasomal degradation and its protein turnover is regulated by the anaphase-promoting complex/cyclosome-Cdh1 (APC/C)
Cdh1
E3 ubiquitin ligase complex. APC/C
Cdh1
acts as a negative stabilizer of
FAH
protein by promoting
FAH
polyubiquitination and decreases the half-life of
FAH
protein. Thus, we envision that Cdh1 might be a key factor in the maintenance of
FAH
protein level to regulate
FAH
-mediated physiological functions.
...
PMID:E3 Ubiquitin Ligase APC/C
Cdh1
Negatively Regulates FAH Protein Stability by Promoting Its Polyubiquitination. 3321 90
