It has been shown that Plzf suppresses aurora kinase C promoter activity in SW480 cells. Therefore, we fur ther examined whether Znf179 affected the transcriptional repression activity of Plzf on aurora kinase C promoter. Our results showed that HA Plzf inhibited aurora kinase C promoter activity in SW480 cell. However, we did not observe selleck chemicals changes in the aurora kinase C pro moter activities following cotransfection of Plzf with Znf179 or control vector. Znf179 regulates the expression of Plzf at protein level The stability of Plzf was reported to be regulated by its interacting protein. In that study, Jin and co workers have demonstrated that KLK4 interacted with Plzf and decreased its protein stability. We therefore examined whether Znf179 interacted with Plzf and con tribute to its protein stability.
Cotransfection of Znf179 resulted in a significant increase in the protein level of ectopically expressed Plzf. Further analysis by quantitative real time RT PCR demon strated that mRNA level of Plzf was not changed in the presence of Znf179. These results suggest that Znf179 interact and regulate Plzf expression at posttranscriptional level. zinc fingers. The N terminal BTB POZ domain is re quired for homo heterodimerization, nuclear localization, and direct binding of corepressors. However, our results showed that the region containing the first two zinc fingers of Plzf is critical for the interaction with Znf179. Although zinc finger domains fre quently bind DNA, there are many examples in which zinc finger domains participate in protein protein interac tions.
Previous studies have shown that the region containing the first three N terminal zinc fingers of Plzf are required and sufficient for Plzf to bind retinoic acid re ceptor. The interaction of Plzf with RAR de creases the ability of RAR to dimerize with retinoid X receptor and diminished the transcriptional activity of RAR. The zinc fingers of Plzf are also involved in interaction of Plzf with other proteins, such as GATA2 and proHB EGF. We have also observed that Znf179 interacts with Plzf and results in increase the ec topic expression of Plzf at posttranscriptional level. How ever, the repressions of Gal4 luciferase reporter and Discussion Znf179 is an evolutionarily highly conserved RING fin ger protein, suggesting an important function of this gene.
In our previous study, we first provide evidence showing functions of Znf179 in neuronal differentiation. The AV-951 potential function of Znf179 at molecular level is further examined by a yeast two hybrid screen which has identified Plzf as a Znf179 interacting protein. Our results suggest that the C terminal but not N terminal fragment of Znf179 interacts with the first two zinc fingers of Plzf. The result also shows that Plzf possess an autonomous ac tivating activity, which this autonomous activa tion of Plzf is consistent to previous report. In that study, Gao et al.