Plzf is a transcriptional regulator that can both repress and activate gene expression. The function of Plzf may depend on its interaction partners in cells. In the study of David et al. Plzf represses transcription by recruiting a histone deacetylase selleck chemicals Gemcitabine through the SMRT mSin3 HDAC co repressor complex. In contrast, Plzf is found to activate GATA4 transcription by binding to angiotensin II activated AT2 receptor. Plzf contains an N terminal BTB POZ domain and nine kruppel like C2H2 aurora kinase C promoter activity by Plzf are not different in the presence of Znf179 or not. We speculate that, first, the protein level of ectopic Plzf expression in the Plzf transfected only cells may be enough for the maximal sup pression. Second, Znf179 indeed affects the ability of Plzf to regulate aurora kinase C promoter activity.

However, the effect of Znf179 on Plzf repression activity is compen sated by the increase of Plzf protein. However, it is still possible that Znf179 may affect the ability of Plzf to regu late specific downstream target genes. Plzf is subject to several different post translational modifications, including phosphorylation, acetylation and conjugation to ubiquitin and SUMO 1. Btbd6a was found to promote the relocation of Plzf from nucleus to cytoplasm and targets Plzf for ubiquitination and deg radation. In contrast, the deubiquitinating enzyme USP37 interacts with Plzf which increases Plzf protein sta bility. In addition, Plzf is found to be phosphorylated by CDK2 on Ser197 and Thr282 and this phosphorylation results in a decrease in protein stability.

In our study, we have found that Znf179 interacts with Plzf and in creases the ectopic expression of Plzf at posttranscrip tional level. It is possible that interaction of Plzf with Znf179 may affect its interaction with other protein and or alters its post translational modification, which results in an increase of the Plzf protein. The expression of the Znf179 gene is restricted to the brain and is regulated during brain development. However, the Plzf is widely expressed in neural progenitors and functions to inhibit neurogenesis. The interaction and reciprocal regulation between Znf179 and Plzf during the neurogenesis is an important issue. Znf179 is a RING finger protein with a characteristic C3HC4 motif located in the N terminus.

It is known that many RING finger proteins act as E3 ubiquitin ligases and are AV-951 associated with the ubiquitin proteasome pathway. In human genome, more than 600 RING finger proteins were annotated as E3s. Whether Znf179 functions as an E3 ubiquitin lig ase needs to be further investigated. Our results reveal that Znf179 interacts with Plzf and increased Plzf expression at posttranscriptional level. In other words, if Znf179 func tions as an E3 ubiquitin ligase, Plzf may not be its sub strate. Plzf is found to be an adaptor of E3 ligase cullin 3. In the study of Mathew et al.