 |
| |
Presenters: Dongsheng Guo (Dr. Janardan Reddy Lab) and Amanda Bass-Zubek (Dr. Kathleen Green Lab) |
|
|
|
|
| |
Dongsheng Guo
|
|
| |
• Dr. Janardan Reddy Lab • Post Doctoral Fellow
|
|
| |
Topic:
|
|
"Peroxisome proliferator-activated receptor (PPAR)-binding protein (PBP):
a crucial coactivator for constitutive androstane receptor (CAR)" |
|
| |
|
|
The nuclear receptor CAR mediates the response evoked by a class of exnobiotics known as Phenobarbital (PB)- like inducers. Target deletion of PBP in hepatocytes (PBPLiv-/-) results in the abrogation of hypertrophic and hyperplastic influences in liver mediated by CAR ligands, Phenobarbital and 1,4-bis-2[-(3,5-dichloropyridyloxy)] benzene (TCPOBOP), and of acetaminophen-induced hepatotoxicity in large part due to the failure to induce CAR target genes. It is known that CAR-ligands such as Phenobarbital and TCPOBOP facilitate the translocation of CAR into the hepatocyte nucleus and this translocation fails to occur in PBP hepatocytes. Recently, we used adenoviral-directed expression of EGFP-CAR in the livers of mice and confirmed that even if there is overexpression of CAR in liver cells, it does not translocate to the nucleus in the absence of PBP but readily occurs in livers of wild type in response to Phenobarbital. These observations clearly show that coactivator PBP is not only an important component of CAR –regulated gene transcription but is also necessary for the translocation of this receptor from cytoplasm to the nucleus.
|
|
|
|
|
 |
|
|
|
|
|
| |
Amanda Bass-Zubek
|
|
| |
• Dr. Kathleen Green Lab • Post Doctoral Fellow
|
|
| |
Topic:
|
|
"Role of Plakophilin 2 in Protein Kinase C-Regulated Desmoplakin Assembly into Desmosomes" |
|
| |
|
|
Plakophilins (PKPs) are members of the armadillo family that localize to the cytoplasmic plaque of intercellular junctions known as desmosomes, and are essential for maintaining the integrity of tissues such as epithelia and heart. In recent studies of early desmosome assembly events, we demonstrated that PKP2 associates with cytolinker desmoplakin (DP) in assembly-competent desmosome plaque precursors. To address the role of PKP2 in regulating desmosome plaque assembly, we evaluated the impact of siRNA-mediated knock-down of PKP2 on DP dynamics and incorporation into desmosomes. Dramatic impairment of DP localization at cell-cell borders and striking retention of DP along keratin intermediate filaments was observed during PKP2 knock-down. DP behavior during PKP2 knock-down strongly resembled that observed during chemical inhibition of Protein Kinase C (PKC) activity or knock-down of PKCα. Further, phosphorylation of known PKC substrates was increased during PKP2 knock-down, without consistent changes in phospho-PKC. We propose that PKP2 provides a scaffold which recruits active PKC to plaque precursors resulting in DP phosphorylation and modulation of DP-IF interactions thereby facilitating precursor translocation and incorporation into desmosomes.
|
|
|
|
|
|
|
|
|
|
|
| |
When:
|
|
Monday, October 2, 2006
12:00PM – 1:00PM
|
|
| |
Location:
|
|
Baldwin Auditorium
Robert H. Lurie Medical Research Center
303 East Superior Street, 1st floor |
