A novel RING finger protein, Znf179, modulates cell cycle exit and neuronal differentiation of P19 embryonal carcinoma cells

Abstract

Znf179 is a member of the RING finger protein family. During embryogenesis, Znf179 is expressed in a restricted manner in the brain, suggesting a potential role in nervous system development. In this report, we show that the expression of Znf179 is upregulated during P19 cell neuronal differentiation. Inhibition of Znf179 expression by RNA interference significantly attenuated neuronal differentiation of P19 cells and a primary culture of cerebellar granule cells. Using a microarray approach and subsequent functional annotation analysis, we identified differentially expressed genes in Znf179-knockdown cells and found that several genes are involved in development, cellular growth, and cell cycle control. Flow cytometric analyses revealed that the population of G0/G1 cells decreased in Znf179-knockdown cells. In agreement with the flow cytometric data, the number of BrdU-incorporated cells significantly increased in Znf179-knockdown cells. Moreover, in Znf179-knockdown cells, p35, a neuronal-specific Cdk5 activator that is known to activate Cdk5 and may affect the cell cycle, and p27, a cell cycle inhibitor, also decreased. Collectively, these results show that induction of the Znf179 gene may be associated with p35 expression and p27 protein accumulation, which lead to cell cycle arrest in the G0/G1 phase, and is critical for neuronal differentiation of P19 cells.

Association of bromodomain BET proteins with chromatin requires dimerization through the conserved motif B

“…Thus, ChIP experiments showed a similar presence of WT or DNmB protein in the promoters, while DmB or Y152KN428A were absent. Addition of retinoic acid (RA) to P19 cells induces cell cycle arrest (Pao et al, 2011). In agreement with results described in Fig.…”

Prdm12 Is Induced by Retinoic Acid and Exhibits Anti-proliferative Properties through the Cell Cycle Modulation of P19 Embryonic Carcinoma Cells

“…It has been reported that RA increases the number of G1 phase cells and the expression of p27 in P19 cells (Sasaki et al, 2000;Pao et al, 2011). In this paper, we described that ectopic Prdm12 has the same function in P19 cells and that RA could induce the expression of Prdm12.…”

Neurolastin, a Dynamin Family GTPase, Regulates Excitatory Synapses and Spine Density

“…Thus, localization of neurolastin to different endocytic vesicles implicates a substantial role in endocytic membrane dynamics. Furthermore, changes in the expression of different endocytic proteins upon shRNA-mediated knockdown of neurolastin have been reported (Pao et al, 2011). Additionally, we find that neurolastin KO mice have smaller endosomes.…”

“…It maps within the chromosomal region encoding the Smith-magenis syndrome (Kimura et al, 1997), a developmental disorder and has known homologs only in higher eukaryotes. Though neurolastin has been shown to be brain-specific with a temporal increase in its expression (Orimo et al, 1998; Pao et al, 2011), there is no direct evidence demonstrating its E3 ligase activity and a very limited understanding about the overall function of this protein. Only recently, a few studies have suggested that neurolastin is important for neuronal differentiation and neurogenesis (Lin et al, 2013; Pao et al, 2011).…”