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:C0162871 (
abdominal aortic aneurysm
)
8,664
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
UFD2a is a mammalian homolog of Saccharomyces cerevisiae Ufd2, originally described as an E4 ubiquitination factor. UFD2a belongs to the U-box family of ubiquitin ligases (E3s) and likely functions as both an E3 and E4. We have isolated and characterized the mouse gene (Ube4b) for UFD2a. A full-length (approximately 5700 bp) Ube4b cDNA was isolated and the corresponding gene spans >100 kb, comprising 27 exons. Luciferase reporter gene analysis of the 5(') flanking region of Ube4b revealed that nucleotides -1018 to -943 (relative to the translation initiation site) possess promoter activity. This functional sequence contains two putative
Sp1
binding sites but not a TATA box. Immunoblot and immunohistochemical analyses revealed that UFD2a is expressed predominantly in the neuronal tissues. We also show that UFD2a interacts with VCP (a
AAA
-family ATPase) that is thought to mediate protein folding. These data implicate UFD2a in the degradation of neuronal proteins by the ubiquitin-proteasome pathway.
...
PMID:Characterization of the mouse gene for the U-box-type ubiquitin ligase UFD2a. 1250 83
Abdominal aortic aneurysm
(
AAA
) is a life-threatening vascular disease without an effective pharmaceutical treatment. Liver kinase B1 (LKB1), a tumor suppressor, is a central regulator of cell polarity and energy homeostasis. However, the role of LKB1 in the development of
AAA
has not been explored. In this study, mice with knockout of smooth muscle-specific LKB1 (LKB1
SMKO
) were generated by cross-breeding LKB1
flox/flox
mice with SM22-CreER
T2
transgenic mice and induced in adult mice by tamoxifen treatment. LKB1 deficiency increased the expression of matrix metalloproteinase 2 (MMP-2), which was inhibited by LKB1 overexpression. Mechanistically, LKB1 could bind to the MMP-2 transcription factor,
specificity protein 1
(
Sp1
), thereby reducing the binding of
Sp1
to the MMP-2 promoter to inhibit MMP-2 expression. LKB1 expression was significantly reduced in abdominal aortas of the mouse
AAA
model. Moreover, smooth muscle-specific LKB1 deletion exaggerated angiotensin II-induced
AAA
formation accompanied by increased
AAA
incidence and aortic expansion. Finally, LKB1 level was significantly lower and MMP-2 level higher in human
AAA
samples than adjacent nonaneurysmal aortic sections. Thus, these results suggest that LKB1 may play a protective role in
AAA
formation by inhibiting MMP-2 expression and could be a potential therapeutic target for
AAA
disease.
...
PMID:Smooth muscle-specific LKB1 deletion exaggerates angiotensin II-induced abdominal aortic aneurysm in mice. 3093 96
