Biomedical subjects

Junghyun Hahn

Publications and source records attributed to Junghyun Hahn.

4 recordsLinked to original sources

PubMed2007

Apoptosis induction and growth suppression by U19/Eaf2 is mediated through its ELL-binding domain.

BACKGROUND: U19/Eaf2 is an androgen-response gene and its downregulation is frequently observed in advanced human prostate cancer. U19/Eaf2 interacts with ELL, a fusion partner of MLL in the (11;19) (q23;p13.1) translocation in acute myeloid leukemia. U19/Eaf2 overexpression induces apoptosis and suppresses xenograft tumor growth. METHODS: Transfection and colony formation were used to assay for apoptosis and growth suppression of various U19/Eaf2 mutants. Co-immunoprecipitation was performed to test the interaction between the U19/Eaf2 constructs and ELL. RESULTS: The region of U19/Eaf2 essential for apoptosis and growth suppression was mapped to amino acids 68-113. This region was necessary and sufficient for binding ELL. Co-expression of U19/Eaf2 and ELL in 293 cells lead to significant increase in cell death and growth suppression. CONCLUSIONS: These observations argue that the interaction with ELL is essential for the induction of apoptosis and growth suppression by U19/Eaf2.

Apoptosis↗

PubMed2006

D2 autoreceptors chronically enhance dopamine neuron pacemaker activity.

Activation of D2 autoreceptors on midbrain dopamine neurons has been shown previously to acutely open K+ channels to inhibit intrinsically generated pacemaker activity. Here we report that D2 autoreceptors act chronically to produce an opposite action: to increase the speed and regularity of repetitive action potential firing. Voltage-, current-, and dynamic-clamp experiments, using conventional whole-cell and perforated patch-clamp recording, with cultured rat midbrain dopamine neurons show that a change in the number of functional A-type K+ channels alters firing rate and susceptibility to irregularity produced by other channels. cAMP and protein kinase A mediate the long-term action of D2 receptors in a manner that counters the short-term effect of this signaling pathway on K+ channel gating. We conclude that D2 autoreceptors, in addition to mediating acute negative feedback, are responsible for long-term enhancement of the rate and fidelity of dopamine neuron pacemaker activity.

Action Potentials↗

PubMed2003

Long-term K+ channel-mediated dampening of dopamine neuron excitability by the antipsychotic drug haloperidol.

Antipsychotic drugs require days of treatment to begin to produce therapeutic effects. We report that in vivo treatment with the antipsychotic drug haloperidol acts with a delay of days to slow spontaneous repetitive firing by isolated midbrain dopamine neurons. The decreased excitability is caused by an increased number of functional A-type K+ channels without any change in gating properties. Upregulation of dopamine neuron Kv4.3 mRNA accounts for this effect, demonstrating a role for channel gene expression in this delayed drug action. The resultant long-term dampening of dopamine neuron excitability may serve to tone down the dopamine system.

Action Potentials↗

PubMed2003

Identification and characterization of a ligand-regulated nuclear export signal in androgen receptor.

Androgen receptor (AR) belongs to the steroid receptor superfamily that regulates gene expression in a ligand-dependent fashion. AR is localized to the cytoplasm in the absence of androgen and translocates into the nuclei to activate gene expression in the presence of ligand. Regulation of AR nuclear import and export represents an essential step in androgen action. A nuclear localization signal (NLS) has been identified in the DNA-binding domain and hinge region of AR and other steroid receptors. Studies on nuclear export of AR, however, are limited, and what might be the underlying mechanism regulating the intracellular localization of steroid receptors is unclear. Our studies have identified a leptomycin B-insensitive nuclear export signal (NESAR) in the ligand-binding domain of AR, which is active in the absence of androgen and repressed upon ligand binding. Consistent with its androgen-sensitivity, NESAR contains amino acid residues in the immediate vicinity of the bound ligand. NESAR is necessary for AR nuclear export and is dominant over the NLS in the DNA-binding domain and hinge region in the absence of hormone. Our findings suggest that androgen can regulate NESAR and, subsequently, the NLS of the AR, providing a mechanism by which androgen regulates AR nuclear/cytoplasmic shuttling. Estrogen receptor alpha and mineralocorticoid receptor also contain functional NES, suggesting that this ligand-regulated NES is conserved among steroid receptors.

Active Transport, Cell Nucleus↗