Disease relevance of Hnf4a

• Therefore, the regulatory effect of the C9-Met-DNA is exerted, at least in part, by a CAAAG sequence that can sequester the endogenous inhibitory Tcf-4 and thereby promote transcription of osteopontin, the direct effector of metastasis in this system [1].
• IL-1 beta antagonists or proteasome inhibitors might increase HNF-4 alpha protein levels in the acute-phase response, which could result in increased liver function and survival [2].
• We conclude that the decrease in HNF-4 alpha that occurs in vivo after the administration of LPS may be the result of IL-1 beta-induced degradation, and likely contributes to the liver insufficiency that occurs [2].
• ACBP overexpression in COS-7 or rat hepatoma cells enhanced transactivation of an HNF-4 alpha-dependent luciferase reporter plasmid by 3.2- and 1.6-fold, respectively [3].

High impact information on Hnf4a

• Liver-enriched transcription factor HNF-4 is a novel member of the steroid hormone receptor superfamily [4].
• IL-1 beta resulted in a decrease in HNF-4 alpha levels in HepG2 cells [2].
• Lipopolysaccharide results in a marked decrease in hepatocyte nuclear factor 4 alpha in rat liver [2].
• We show here that lipopolysaccharide (LPS), an endotoxin that induces the acute-phase response, results in a marked decrease in the major isoforms of the transcription factor, hepatocyte nuclear factor 4 alpha (HNF-4 alpha), in livers of rats [2].
• Transfection of an expression vector for Tcf-4 inhibited the stimulated activity of the osteopontin promoter-reporter construct caused by transiently transfected active fragments of Met-DNA or permanently transfected Met-DNA [1].

Biological context of Hnf4a

• The functional significance of ACBP interaction with HNF-4 alpha was evidenced by mammalian two-hybrid and transactivation assays [3].
• (iv) LSCM fluorescence resonance energy transfer determined an intermolecular distance of 53 A between ACBP and HNF-4 alpha in rat hepatoma cell nuclei [3].
• As shown herein for the first time, ACBP in the nucleus physically and functionally interacted with hepatocyte nuclear factor-4 alpha (HNF-4 alpha), a nuclear binding protein that regulates transcription of genes involved in both lipid and glucose metabolism [3].
• RESULTS: Both experimental groups displayed an increase in adiposity with contrasting effects on TG (lowered by fenofibrate and increased by isotretinoin) and gene expression (no change in fibrate-treated rats and increased expression of ApoC-III and Hnf-4 in isotretinoin-treated group) [5].
• In conclusion, beta-catenin and Tcf-4 play a dual role in vascular remodeling by inhibiting VSMC apoptosis and promoting proliferation [6].

Anatomical context of Hnf4a

• HNF4 alpha is an orphan member of the nuclear receptor family with prominent functions in liver, gut, kidney and pancreatic beta cells [7].
• (iii) Double immunolabeling and laser scanning confocal microscopy (LSCM) of rat hepatoma cells and transfected COS-7 cells significantly colocalized ACBP and HNF-4 alpha within the nucleus and in the perinuclear region close to the nuclear membrane [3].
• However, cellular viability, cytoskeleton organization and function, as evaluated by albumin production, ureagenesis, and enzyme activity of cytochrome P450 as well as expression levels of hepatocyte nuclear factor 4 alpha deteriorated [8].

Other interactions of Hnf4a

• This decrease was of functional significance, because expression of a gene that is highly dependent on HNF-4 alpha, HNF-1 alpha, was reduced [2].
• Physical and functional interaction of Acyl-CoA-binding protein with hepatocyte nuclear factor-4 alpha [3].

Analytical, diagnostic and therapeutic context of Hnf4a

• (v) Immunogold electron microscopy detected ACBP within 43 A of HNF-4 alpha [3].

References