Scientific article

Primate-specific RFPL1 gene controls cell-cycle progression through cyclin B1/Cdc2 degradation

Published inCell death and differentiation, vol. 18, no. 2, p. 293-303
Publication date2011

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.

  • 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
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
Main files (1)
Article (Published version)
ISSN of the journal1350-9047

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