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The tumour suppressor ARF is specifically required for p53 activation under oncogenic stress. Recent studies showed that p53 activation mediated by ARF, but not that induced by DNA damage, acts as a major protection against tumorigenesis in vivo under certain biological settings, suggesting that the ARF-p53 axis has more fundamental functions in tumour(More)
The anterior cruciate ligament (ACL) inserts into bone through a characteristic fibrocartilagenous interface, which is essential for load transfer between soft and hard tissues. This multi-tissue interface is lost post ACL reconstruction, and the lack of an anatomic fibrocartilage interface between graft and bone remains the leading cause of graft failure.(More)
ABCA7 is homologous to ABCA1 and has recently been shown in cell culture to bind apolipoprotein A-I (apoA-I) and to promote the efflux of phospholipids. However, it is not known if ABCA7 promotes lipid efflux in vivo. When expressed in HEK293 cells, both human and mouse ABCA7 promoted phospholipid efflux to apoA-I but no detectable cholesterol efflux.(More)
The cyclin D1 proto-oncoprotein is a crucial regulator in cell-cycle progression, and aberrant overexpression of cyclin D1 is linked to tumorigenesis of many different cancer types. By screening ubiquitinated cyclin D1 as a substrate with a deubiquitinase library, we have identified USP2 as a specific deubiquitinase for cyclin D1. USP2 directly interacts(More)
We recently identified aberrant cytoplasmic expression of nucleophosmin (NPM) as the immunohistochemical marker of a large subgroup of acute myeloid leukemia (AML) (about one-third of adult AML) that is characterized by normal karyotype and mutations occurring at the exon-12 of the NPM gene. In this paper, we have elucidated the molecular mechanism(More)
Barrett's esophagus is characterized by a distinct Th2-predominant cytokine profile (IL-4) from in vivo or ex vivo evidence. The detailed role of cytokines in Barrett's esophagus, particularly whether Th2 cytokines are causative factors driving metaplastic processes, remains unknown. In this study, air-liquid interface-cultured human esophageal epithelial(More)
Immune-mediated injury by the protease-activated receptor-2-interleukin-8 (PAR-2-IL8) pathway may underlie the development of gastroesophageal reflux disease (GERD). However, the localization of PAR-2 and the mechanism of PAR-2 activation remain unclear. This study aimed to address these questions on an esophageal stratified squamous epithelial model and in(More)
We determined the role of N-linked glycosylation of apolipoprotein B (apoB) in the assembly and secretion of lipoproteins using transfected rat hepatoma McA-RH7777 cells expressing human apoB-17, apoB-37, and apoB-50, three apoB variants with different ability to recruit neutral lipids. Substituting Asn residue with Gln at the single glycosylation site(More)
The PTEN tumor suppressor is a lipid phosphatase that has a central role in regulating the phosphatidylinositol-3-kinase (PI3K) signal transduction cascade. Nevertheless, the mechanism by which the PTEN activity is regulated in cells needs further elucidation. Although previous studies have shown that ubiquitination of PTEN can modulate its stability and(More)
We examined the role of S-linked palmitoylation of human apolipoprotein (apo) B in the assembly and secretion of very low density lipoproteins using recombinant human apoB48. There are four free cysteine residues (Cys(1085), Cys(1396), Cys(1478), and Cys(1635)) within apoB48 that potentially can be palmitoylated. All four cysteine residues were substituted(More)