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Primate-specific RFPL1 gene controls cell-cycle progression through cyclin B1/Cdc2 degradation |
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Published in | Cell death and differentiation. 2011, vol. 18, no. 2, p. 293-303 | |
Abstract | Ret finger protein-like 1 (RFPL1) is a primate-specific target gene of Pax6, a key transcription factor for pancreas, eye and neocortex development. However, its cellular activity remains elusive. In this article, we report that Pax6-elicited expression of the human (h)RFPL1 gene in HeLa cells can be enhanced by in vivo p53 binding to its promoter and therefore investigated the hypothesis that hRFPL1 regulates cell-cycle progression. Upon expression in these cells, hRFPL1 decreased cell number through a kinase-dependent mechanism as PKC activates and Cdc2 inhibits hRFPL1 activity. hRFPL1 antiproliferative activity led to an increased cell population in G(2)/M phase and specific cyclin B1 and Cdc2 downregulations, which were precluded by a proteasome inhibitor. Specifically, cytoplasm-localized hRFPL1 prevented cyclin B1 and Cdc2 accumulation during interphase. Consequently, cells showed a delayed entry into mitosis and cell-cycle lengthening resulting from a threefold increase in G(2) phase duration. Given previous reports that RFPL1 is expressed during cell differentiation, its impact on cell-cycle lengthening therefore provides novel insights into primate-specific development. | |
Keywords | Animals — Carrier Proteins/genetics/metabolism/physiology — Cell Division — Cyclin B/metabolism — Cyclin B1/metabolism — Eye Proteins/metabolism — G2 Phase — HeLa Cells — Homeodomain Proteins/metabolism — Humans — Interphase — Mitosis — Paired Box Transcription Factors/metabolism — Primates/metabolism — Promoter Regions, Genetic — Protein Binding — Protein Kinase C/metabolism — Repressor Proteins/metabolism — Tumor Suppressor Protein p53/metabolism | |
Identifiers | DOI: 10.1038/cdd.2010.102 PMID: 20725088 | |
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Research group | Radicaux libres et cellules souches embryonnaires (60) | |
Citation (ISO format) | BONNEFONT, Jérôme et al. Primate-specific RFPL1 gene controls cell-cycle progression through cyclin B1/Cdc2 degradation. In: Cell death and differentiation, 2011, vol. 18, n° 2, p. 293-303. doi: 10.1038/cdd.2010.102 https://archive-ouverte.unige.ch/unige:25091 |