title: 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.
authors.affiliation: Institute of Bioinformatics and Biosignal Transduction, College of Bioscience and Biotechnology, National Cheng Kung University, Tainan, Taiwan.
authors.forename: P-C
authors.initials: PC
authors.lastname: Pao
authors.forename: N-K
authors.initials: NK
authors.lastname: Huang
authors.forename: Y-W
authors.initials: YW
authors.lastname: Liu
authors.forename: S-H
authors.initials: SH
authors.lastname: Yeh
authors.forename: S-T
authors.initials: ST
authors.lastname: Lin
authors.forename: C-P
authors.initials: CP
authors.lastname: Hsieh
authors.forename: A-M
authors.initials: AM
authors.lastname: Huang
authors.forename: H-S
authors.initials: HS
authors.lastname: Huang
authors.forename: J T
authors.initials: JT
authors.lastname: Tseng
authors.forename: W-C
authors.initials: WC
authors.lastname: Chang
authors.forename: Y-C
authors.initials: YC
authors.lastname: Lee
mesh_terms: D000818:Animals; D001973:Bromodeoxyuridine / Q000494:pharmacology; D002454:Cell Differentiation; D002478:Cells, Cultured; D051360:Cyclin-Dependent Kinase 5 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D054278:Embryonal Carcinoma Stem Cells / Q000166:cytology* / Q000378:metabolism; D016193:G1 Phase; D059585:G1 Phase Cell Cycle Checkpoints; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D055495:Neurogenesis / Q000235:genetics; D009474:Neurons / Q000166:cytology* / Q000378:metabolism; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D016192:Resting Phase, Cell Cycle; D014212:Tretinoin / Q000494:pharmacology
chemical_list: D004268:DNA-Binding Proteins; D034741:RNA, Small Interfering; C113383:ZNF179 protein, mouse; D050760:Cyclin-Dependent Kinase Inhibitor p27; D014212:Tretinoin; D051360:Cyclin-Dependent Kinase 5; D001973:Bromodeoxyuridine