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Cell Death Differ. 2011 Feb;18(2):293-303. doi: 10.1038/cdd.2010.102. Epub 2010 Aug 20.

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

Author information

1
Department of Pathology and Immunology, School of Medicine, University of Geneva, Rue Michel-Servet 1, Geneva, Switzerland.

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.

PMID:
20725088
PMCID:
PMC3131898
DOI:
10.1038/cdd.2010.102
[Indexed for MEDLINE]
Free PMC Article

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