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: UNIPROT:A7BJS8 (
F-box and WD40 domain protein 7
)
5
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
FBXW7 (
F-box and WD40 domain protein 7
) is a tumor suppressor frequently inactivated in human cancers. The precise molecular mechanisms by which FBXW7 exerts antitumor activity remain under intensive investigation and are thought to relate in part to FBXW7-mediated destruction of key
cancer
-relevant proteins. Enolase 1 (ENO1) possesses oncogenic activity and is often overexpressed in various human cancers, besides its critical role in glycolysis. However, the detailed regulatory mechanisms of ENO1 expression remain unclear. Here we show that the elevated expression of ENO1 was identified in FBXW7-depletion HCT116 cells through two-dimensional protein electrophoresis and mass spectrometry assays (2DE-MS). Subsequent western blotting and immunohistochemical assays confirmed that ENO1 expression reversely correlates with FBXW7 expression in several cells and colon cancer tissues. Furthermore, we show that FBXW7 physically binds to ENO1 and targets ENO1 for ubiquitin-mediated degradation. Functionally, we found that FBXW7 suppresses the ENO1-induced gene expression, lactate production, cell proliferation and migration. These findings suggest that ENO1 is a novel substrate of FBXW7, and its activity can be negatively regulated by FBXW7 at the posttranslational level. Our work provides a novel molecular insight into FBXW7-directed tumor suppression through regulation of ENO1.
...
PMID:FBXW7 negatively regulates ENO1 expression and function in colorectal cancer. 2609 98
F-box and WD40 domain protein 7
(
FBXW7
) is a component of the SKP1-CUL1-F-box protein (SCF) complex that mediates the ubiquitination of diverse oncogenic target proteins. The exploration of
FBXW7
mutations in human primary
cancer
has revealed three mutation hotspots at conserved arginine residues (Arg
465
, Arg
479
, and Arg
505
) in the WD40 domain, which are critical for substrate recognition. To study the function of human
FBXW7
R465C
, the most frequent mutation in human
malignancies
, we generated a novel conditional knockin mouse line of murine Fbxw7
R468C
corresponding to human
FBXW7
R465C
. Systemic heterozygous knockin of the Fbxw7
R468C
mutation resulted in perinatal lethality due to defects in lung development, and occasionally caused an eyes-open at birth phenotype and cleft palate. Furthermore, mice carrying liver-specific heterozygous and homozygous Fbxw7
R468C
alleles cooperated with an oncogenic Kras mutation to exhibit bile duct hyperplasia within 8 months of birth and cholangiocarcinoma-like lesions within 8 weeks of birth, respectively. In addition, the substrates affected by the mutant Fbxw7 differed between the embryos, embryonic fibroblasts, and adult liver. This novel conditional knockin Fbxw7
R468C
line should be useful to gain a more profound understanding of carcinogenesis associated with mutation of
FBXW7
.
...
PMID:Establishment and analysis of a novel mouse line carrying a conditional knockin allele of a cancer-specific FBXW7 mutation. 2938 60
